V Cuomo

The American University of Rome, Roma, Latium, Italy

Are you V Cuomo?

Claim your profile

Publications (213)731.78 Total impact

  • Maria Morena, Roozendaal B, Trezza V, Ratano P, Peloso A, Hauer D, Atsak P, Trabace L, Cuomo V, McGaugh JL, Schelling G, Campolongo P.
    [Show abstract] [Hide abstract]
    ABSTRACT: Previous studies have provided extensive evidence that administration of cannabinoid drugs after training modulates the consolidation of memory for an aversive experience. The present experiments investigated whether the memory consolidation is regulated by endogenously released cannabinoids. The experiments first examined whether the endocannabinoids anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) are released by aversive training. Inhibitory avoidance training with higher footshock intensity produced increased levels of AEA in the amygdala, hippocampus, and medial prefrontal cortex (mPFC) shortly after training in comparison with levels assessed in rats trained with lower footshock intensity or unshocked controls exposed only to the training apparatus. In contrast, 2-AG levels were not significantly elevated. The additional finding that posttraining infusions of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which selectively increases AEA levels at active synapses, administered into the basolateral complex of the amygdala (BLA), hippocampus, or mPFC enhanced memory strongly suggests that the endogenously released AEA modulates memory consolidation. Moreover, in support of the view that this emotional training-associated increase in endocannabinoid neurotransmission, and its effects on memory enhancement, depends on the integrity of functional interactions between these different brain regions, we found that disruption of BLA activity blocked the training-induced increases in AEA levels as well as the memory enhancement produced by URB597 administered into the hippocampus or mPFC. Thus, the findings provide evidence that emotionally arousing training increases AEA levels within prefrontal-limbic circuits and strongly suggest that this cannabinoid activation regulates emotional arousal effects on memory consolidation.
    Proc Natl Acad Sci U S A. 12/2014; 111(52):18333-8.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: It has been well documented that β-amyloid (Aβ) peptide accumulation and aggregation in the brain plays a crucial role in the pathophysiology of Alzheimer’s disease (AD). However, a new orientation of the amyloid cascade hypothesis has evidenced that soluble forms of the peptide (sAβ) are involved in Aβ-induced cognitive impairment and cause rapid disruption of the synaptic mechanisms underlying memory. The primary aim of this study was to elucidate the effects of sAβ, acutely injected intracerebrally (i.c.v., 4 μM), on the short term and long term memory of young adult male rats, by using the novel object recognition task. Glutamatergic receptors have been proposed as mediating the effect of Aβ on synaptic plasticity and memory. Thus, we also investigated the effects of sAβ on prefrontal cortex (PFC) glutamate release and the specific contribution of N-methyl-D-aspartate (NMDA) receptor modulation to the effects of sAβ administration on the cognitive parameters evaluated. We found that a single i.c.v. injection of sAβ 2 h before testing did not alter the ability of rats to differentiate between a familiar and a novel object, in a short term memory test, while it was able to negatively affect consolidation/retrieval of long term memory. Moreover, a significant increase of glutamate levels was found in PFC of rats treated with the peptide 2 h earlier. Interestingly, memory deficit induced by sAβ was reversed by a NMDA-receptor antagonist, memantine (5 mg/kg i.p), administered immediately after the familiarization trial (T1). On the contrary, memantine administered 30 min before T1 trial, was not able to rescue long term memory impairment. Taken together, our results suggest that an acute i.c.v. injection of sAβ peptide interferes with the consolidation/retrieval of long term memory. Moreover, such sAβ-induced effect indicates the involvement of glutamatergic system, proposing that NMDA receptor inhibition might prevent or lead to the recovery of early cognitive impairment. http://journal.frontiersin.org/Journal/10.3389/fnbeh.2014.00332/full#h1
    Frontiers in Behavioral Neuroscience 09/2014; 8(332). · 4.16 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Genetic and environmental factors play an important role in the cannabinoid modulation of motivation and emotion. Therefore, the aim of the present study was to test whether anandamide modulation of social behavior is strain- and context-dependent. We tested the effects of the anandamide hydrolysis inhibitor URB597 on social behavior and 50-kHz ultrasonic vocalizations (USVs) in adolescent and adult Wistar and Sprague–Dawley rats tested in different emotionally arousing conditions (familiarity/unfamiliarity to the test cage, low/high light). Under all experimental conditions, adolescent and adult Sprague–Dawley rats displayed higher levels of social behavior and emitted more 50-kHz USVs than Wistar rats. URB597 enhanced social play behavior in adolescent Wistar rats under all experimental conditions. However, URB597 only increased social interaction in adult Wistar rats under unfamiliar/high light conditions. URB597 did not affect adolescent social play behavior and adult social interaction in Sprague–Dawley rats under any experimental condition. Moreover, URB597 increased the USVs emitted during social interaction by adolescent Wistar and adult Sprague–Dawley rats tested under familiar/high light and unfamiliar/high light, respectively. These results show that anandamide has distinct roles in adolescent and adult social behaviors. Anandamide modulation of adolescent social play behavior is strain- but not context-dependent. Conversely, anandamide modulation of adult social behavior and USV emission depends upon both strain and experimental context. Furthermore, these results confirm that profound behavioral differences exist between Wistar and Sprague–Dawley rats, which may explain the sometimes contradictory effects of cannabinoid drugs on emotionality in different strains of rodents.
    European Neuropsychopharmacology 08/2014; · 5.40 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The new-released Diagnostic and Statistical Manual of Mental Disorders (DSM-5) defines post-traumatic stress disorder (PTSD) as a "trauma and stressor-related disorder". PTSD pathogenesis relies on paradoxical changes of emotional memory processing induced by the trauma exposure and associated with emotional dysfunction. Several animal models of PTSD have been validated and are currently used. Each one mimics a particular subset of the disorder with particular emphasis, mainly driven by the past classification of PTSD in the DSM-4, on the emotional features. In view of the recent update in the DSM-5, our aim was to develop, by using well-validated paradigms, a modified model of PTSD able to mimic at the same time both the cognitive and emotional features of the disease. We exposed male rats to either a piece of worn cat collar or to a series of inescapable footshocks paired with a PTSD risk factor, i.e., social isolation. Animals were subsequently re-exposed to the conditioned contexts at different time intervals in order to test memory retention for the stressors. In addition, footshock-exposed rats were tested in the elevated-plus-maze and social interaction tests. We found that rats exposed to a cat collar exhibited an acute fear response that did not lead to enduring memory retention. Conversely, footshock-exposed rats expressed a successful retention of the stressful experience at 1, 7, 14, 21 and 56 post-exposure days. Footshock-exposed rats displayed an anxious behavioral profile in the social interaction test and a significantly reduced locomotor activity in the elevated-plus-maze test. These dysfunctions were not observed when animals were socially housed, thus highlighting a social buffering effect in the development of the pathology. Our results underline the good validity of a footshock-based paradigm paired with social isolation as a PTSD animal model, able to mimic at the same time both some of the enduring cognitive and emotional facets of the pathology.
    Frontiers in Behavioral Neuroscience 04/2014; 8:142. · 4.16 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Data in animal models and surveys in humans have revealed psychiatric complications of long-term anabolic androgenic steroid abuse. However, the neurobiochemical mechanisms behind the observed behavioral changes are poorly understood.The aim of the present study was to investigate the effects of nandrolone decanoate on emotional behavior and neurochemical brain alterations in gonadally intact male rats.The behavioral reactivity to the elevated plus maze and the social interaction test was used to assess anxiety-related symptoms, and the sucrose preference test was used to evaluate anhedonia. Dopaminergic, serotonergic and noradrenergic transmissions were also evaluated in selected brain areas.The chronic administration of nandrolone, at 5 mg kg−1 injected daily for 4 weeks, induced the loss of sweet taste preference, a sign of anhedonia and dysfunction of the reward pathway. The behavioral outcomes were accompanied by reductions in the dopamine, serotonin and noradrenaline contents in the nucleus accumbens. Alterations in the time spent in the open arms and in the social interaction test were not found, suggesting that nandrolone did not induce an anxiogenic profile. No differences were revealed between the experimental groups in the amygdala in terms of the neurotransmitters measured.Our data suggest that nandrolone-treated rats have a depressive, but not anxiogenic-like, profile, accompanied by brain region-dependent changes in dopaminergic, serotonergic and noradrenergic neurotransmission. As anabolic androgenic steroid dependence is plausibly the major form of worldwide substance dependence that remains largely unexplored, it should be highlighted that our data could contribute to a better understanding of the altered rewards induced by nandrolone treatment and to the development of appropriate treatments.
    Steroids 01/2014; 79:7–13. · 2.72 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Social play behavior is the most characteristic social behavior in young mammals. It is highly rewarding and crucial for proper neurobehavioral development. Despite the importance of genetic factors in normal and pathological social behaviors, little information is available about strain influences on social play. The aim of this study was to investigate differences in social play behavior, 50-kHz ultrasonic vocalizations (USVs) and their modulation by acute morphine and amphetamine administration in two rat strains widely used in behavioral pharmacology studies, i.e., Wistar and Sprague-Dawley rats. Sprague-Dawley rats showed higher levels of social play than Wistar rats. In both strains, no correlation was found between the performance of social behaviors and the emission of 50-kHz USVs. In Wistar and Sprague-Dawley rats, morphine increased and amphetamine decreased social play. The effects of morphine, however, were more pronounced in Wistar than Sprague-Dawley animals. In both strains, morphine did not affect USV emission, while amphetamine increased it during cage exploration. In Sprague-Dawley rats only, amphetamine decreased USVs during social interaction. Wistar and Sprague-Dawley rats differ in their absolute levels of social play behavior and 50-kHz USVs, and quantitative differences exist in their response to pharmacological manipulations of social play. The emission of 50-kHz USVs and the behavioral parameters thought to reflect rewarding social interactions in adolescent rats are dissociable.
    Psychopharmacology 11/2013; · 3.99 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Anandamide (AEA) is an endogenous cannabinoid catalyzed by the enzyme fatty acid amide hydrolase (FAAH). FAAH Inhibitors significantly increase AEA brain levels thereby potentiating its effects at CB1 receptors. Among FAAH inhibitors a potent and selective inhibitor is URB597, which elicits marked anxiolytic-like and antidepressant-like responses in rodent models. Exploring the neurochemical effects of URB597 in the brain appears to be crucial to understand its mechanism of action. In this study, we evaluated the effect of URB597 on the hypothalamus-pituitary-adrenal axis of adult male Wistar stressed rats. Animals pre-treated with URB597 (0.1mg/Kg and 0.3 mg/Kg) were forced to swim for 20 min. Immediately (20 min) and 20 min after stress (40 min), animals were decapitated. Plasma corticosterone (CORT) levels and quantitative expressions of the c-fos and corticotropin releasing factor (CRF) in the brain and of the pro-opiomelanocortin (POMC) mRNA in the hypophysis were measured by in situ hybridization. Plasma CORT was significantly increased in stressed rats and URB957 treatment caused a slight dose-dependent decrease of these levels that did not reach the statistical significance. Stress significantly increased c-fos mRNA expression in paraventricular nucleus of hypothalamus (PVN), basolateral amygdala (BLA), central amygdala (CeA), medial amygdala (MeA), locus coeruleus (LC) and nucleus of solitary tract (NTS). In stressed rats URB597 treatment caused a significant decrease in c-fos mRNA expression in PVN at 20 min with both doses and at 40 min only with 0.3 mg/Kg dose. In BLA, both dosages of URB597 significantly decreased c-fos levels at 40 min. URB597 0.3 mg/kg treatment significantly decreased c-fos levels at 40 min in the CeA, while the decrease was evident at both 20 and 40 min in the MeA. Conversely, URB597 0.1mg/kg treatment caused a significant increase of c-fos mRNA in LC at 20 min while in NTS both dosage of URB597 induced an increase of c-fos at the same time point. The expression of CRF mRNA was increased in the PVN of stressed rats sacrificed at 40 min. Both dosages of URB597 prevented such increase. POMC mRNA in adenohypophysis was significantly increased in stressed rats compared to controls at both 20 and 40 min. URB597, significantly and dose dependently, prevented such increase at 40 min. These results suggest that URB597 treatment modulated the activation of key brain areas induced by stress, such as the PVN, amygdala, LC and NTS. These effects were accompanied by the prevention of CRF and POMC over-expression, suggesting a direct or indirect involvement of each area and probably reflecting the differences in terms of FAAH and CB1 expression.
    Society for Neuroscience, San Diego, USA; 11/2013
  • [Show abstract] [Hide abstract]
    ABSTRACT: The endocannabinoid system has gained much attention as a new potential pharmacotherapeutic target in various neurodegenerative diseases, including Alzheimer’s disease (AD). However, the association between CB1 alterations and the development of AD neuropathology is unclear and often contradictory. In this study, brain CB1 mRNA and CB1 protein levels were analyzed in 3×Tg-AD mice and compared to wild-type littermates at 2, 6 and 12 months of age, using in-situ hybridization and immunohistochemistry, respectively. Semiquantitative analysis of CB1 expression focused on the prefrontal cortex (PFC), prelimbic cortex, dorsal hippocampus (DH), basolateral amygdala complex (BLA), and ventral hippocampus (VH), all areas with high CB1 densities that are strongly affected by neuropathology in 3×Tg-AD mice. At 2 months of age, there was no change in CB1 mRNA and protein levels in 3×Tg-AD mice compared to Non-Tg mice in all brain areas analyzed. However, at 6 and 12 months of age, CB1 mRNA levels were significantly higher in PFC, DH, and BLA, and lower in VH in 3×Tg-AD mice compared to wild-type littermates. CB1 immunohistochemistry revealed that CB1 protein expression was unchanged in 3×Tg-AD at 2 and 6 months of age, while a significant decrease in CB1 receptor immunoreactivity was detected in the BLA and DH of 12-month-old 3×Tg-AD mice, with no sign of alteration in other brain areas. The altered CB1 levels appear, rather, to be age-and/or pathology-dependent, indicating an involvement of the endocannabinoid system in AD pathology and supporting the ECS as a potential novel therapeutic target for treatment of AD.
    The Italian SocietyOf Pharmacology (SIF), Torino, Italy; 10/2013
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Oleoylethanolamide (OEA) is a gut-derived endogenous lipid that stimulates vagal fibres to induce satiety. Our previous work has shown that peripherally administered OEA activates c-fos transcription in the nucleus of the solitary tract (NST) and in the paraventricular nucleus (PVN) where it enhances oxytocin (OXY) expression. The anorexigenic action of OEA is prevented by the i.c.v. administration of a selective OXY receptor antagonist, suggesting a necessary role of OXYergic mediation of OEA's effect. The NST is the source of direct noradrenergic afferent input to hypothalamic OXY neurons, and we therefore hypothesized that the activation of this pathway might mediate OEA effects on PVN neurons. To test this hypothesis, we subjected rats to intra-PVN administration of the toxin saporin (DSAP) conjugated to an antibody against dopamine-beta-hydroxylase (DBH), to destroy hindbrain noradrenergic neurons. In these rats we evaluated the effects of OEA (10 mg/kg, i.p.) on feeding behavior, on c-Fos and OXY immunoreactivity in the PVN, and on OXY immunoreactivity in the posterior pituitary gland. We found that the DSAP lesion completely prevented OEA's effects on food intake, on Fos and OXY expression in the PVN and on OXY immunoreactivity of the posterior pituitary gland; all effects were maintained in sham operated rats. These results support the hypothesis that noradrenergic NST-PVN projections are involved in the activation of the hypothalamic OXY system which mediates OEA's pro-satiety action.
    AJP Endocrinology and Metabolism 09/2013; · 4.51 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The anandamide monounsaturated analogue oleoylethanolamide (OEA) acts as satiety signal released from enterocytes upon the ingestion of dietary fats to prolong the interval to the next meal. This effect, which requires intact vagal fibers and intestinal PPAR-alpha receptors, is coupled to the increase of c-fos and oxytocin mRNA expression in neurons of the paraventricular nucleus (PVN) and is prevented by the intracerebroventricular administration of a selective oxytocin antagonist, thus suggesting a necessary role of oxytocinergic neurotransmission in the pro-satiety effect of OEA. By brain microdialysis and immunohistochemistry, in this study we demonstrate that OEA treatment can stimulate oxytocin neurosecretion from the PVN and enhance oxytocin expression at both axonal and somatodendritic levels of hypothalamic neurons. Such effects, which are maximum two hours after OEA administration, support the hypothesis that the satiety-inducing action of OEA is mediated by the activation of oxytocin hypothalamic neurons.
    Peptides 08/2013; · 2.61 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Despite the consolidation of the amyloid hypothesis, the main component of senile plaques in Alzheimer's disease (AD), recent findings have led to a conceptual shift opening new questions about the potential physiological role of this peptide. In addition, soluble beta amyloid (BA), in transgenic AD model, resulted increased after chronic and acute stress and alterations in cortisol levels have been reported in AD. Impaired hypothalamic pituitary adrenal (HPA) axis has been linked to depressive state and, consistently, we have previously demonstrated that sBA is able to provoke depressive-like profile in rats. Here we further analysed the effect of the peptide in behavioural paradigms used to study emotional and cognitive response, by using the passive avoidance task, for cognitive parameters, and the sucrose preference test (SPT), to evaluate anhedonia. Moreover, in order to correlate behavioural with neurochemical and neuroendocrinal data, we investigated the effects of the peptide on noradrenergic system in amygdala (AMY), prefrontal cortex (PFC) and hippocampus (HIPP) along with plasmatic corticosterone and hypothalamic corticotrophin releasing factor (CRF). We found that BA-treated animals showed an impaired memory consolidation of inhibitory avoidance training, while no effect was evident in SPT. These results lead us to hypothesize a different response to stress coping behaviour in BA treated rats. Moreover, BA caused a significant increase in NA in PFC and HIPP, while in AMY was decreased. Consistently, we found a significant decrease in plasma corticosterone concentrations in BA-treated rats. Taken together, our data suggest that BA exerts an inhibitory effect on HPA axis activation.
    Current pharmaceutical design 07/2013; · 4.41 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although it is well established that cannabinoid drugs can influence cognitive performance, the findings -describing both enhancing and impairing effects- have been ambiguous. Here, we investigated the effects of posttraining systemic administration of the synthetic cannabinoid agonist WIN55,212-2 (0.1, 0.3 or 1.0 mg/kg) on short- and long-term retention of object recognition memory under two conditions that differed in their training-associated arousal level. In male Sprague-Dawley rats that were not previously habituated to the experimental context, WIN55,212-2 administered immediately after a 3-min training trial biphasically impaired retention performance at a 1-hr interval. In contrast, WIN55,212-2 enhanced 1-hr retention of rats that had received extensive prior habituation to the experimental context. Interestingly, immediate posttraining administration of WIN55,212-2 to non-habituated rats, in doses that impaired 1-hr retention, enhanced object recognition performance at a 24-hr interval. Posttraining WIN55,212-2 administration to habituated rats did not significantly affect 24-hr retention. In light of intimate interactions between cannabinoids and the hypothalamic-pituitary-adrenal axis, we further investigated whether cannabinoid administration might differently influence training-induced glucocorticoid activity in rats in these two habituation conditions. WIN55,212-2 administered after object recognition training elevated plasma corticosterone levels in non-habituated rats whereas it decreased corticosterone levels in habituated rats. Most importantly, following pretreatment with the corticosterone-synthesis inhibitor metyrapone, WIN55,212-2 effects on 1- and 24-hr retention of non-habituated rats became similar to those seen in the low-aroused habituated animals, indicating that cannabinoid-induced regulation of adrenocortical activity contributes to the environmentally sensitive effects of systemically administered cannabinoids on short- and long-term retention of object recognition memory.Neuropsychopharmacology accepted article preview online, 22 January 2013; doi:10.1038/npp.2013.26.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 01/2013; · 8.68 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Aims: Psychosocial stress alters the HPA-axis. Increasing evidence shows a link between these alterations and oxidant elevation. Oxidative stress is implicated in the stress-response and in the pathogenesis of neurologic and psychiatric diseases. NOX enzymes are a major source of ROS in the CNS. Here, we investigated the contributory role of NOX2-derived ROS to the development of neuroendocrine alterations in a rat model of chronic psychosocial stress, the social isolation. Results: Significant elevations in the hypothalamic levels of CRF and plasmatic ACTH were observed from four weeks of social isolation. Increased levels of peripheral markers of the HPA-axis (plasmatic and salivary corticosterone) were observed at later time point of social isolation (seven weeks). Alteration in exploratory activity of isolated rats followed the same time course. Increased expression of markers of oxidative stress (8OhdG and nitrotyrosine) and NOX2 mRNA was early detectable in the hypothalamus of isolated rats (after two weeks), but later (after seven weeks) in the adrenal gland. A three-weeks-treatment with the antioxidant/NOX inhibitor apocynin stopped the progression of isolation-induced alterations of the HPA-axis. Rats with a loss of function mutation in the NOX2 subunit p47phox were totally protected from alterations of the neuroendocrine profile, behavior and increased NOX2 mRNA expression induced by social isolation. Innovation: We demonstrate that psychosocial stress induces early elevation of NOX2-derived oxidative stress in the hypothalamus and consequent alterations of the HPA-axis, leading ultimately to altered behavior. Conclusion: Pharmacological targeting of NOX2 might be of crucial importance for treatment of psychosocial stress-induced psychosis.
    Antioxidants & Redox Signaling 01/2013; · 8.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The brain endocannabinoid system plays a crucial role in emotional processes. We have previously identified an important role for endocannabinoids in social play behavior, a highly rewarding form of social interaction in adolescent rats. Here, we tested the hypothesis that endocannabinoid modulation of social play behavior occurs in brain regions implicated in emotion and motivation. Social play increased levels of the endocannabinoid anandamide in the amygdala and nucleus accumbens (NAc), but not in prefrontal cortex or hippocampus of 4- to 5-week-old male Wistar rats. Furthermore, social play increased phosphorylation of CB1 cannabinoid receptors in the amygdala. Systemic administration of the anandamide hydrolysis inhibitor URB597 increased social play behavior, and augmented the associated elevation in anandamide levels in the amygdala, but not the NAc. Infusion of URB597 into the basolateral amygdala (BLA) increased social play behavior, and blockade of BLA CB1 cannabinoid receptors with the antagonist/inverse agonist SR141716A prevented the play-enhancing effects of systemic administration of URB597. Infusion of URB597 into the NAc also increased social play, but blockade of NAc CB1 cannabinoid receptors did not antagonize the play-enhancing effects of systemic URB597 treatment. Last, SR141716A did not affect social play after infusion into the core and shell subregions of the NAc, while it reduced social play when infused into the BLA. These data show that increased anandamide signaling in the amygdala and NAc augments social play, and identify the BLA as a prominent site of action for endocannabinoids to modulate the rewarding properties of social interactions in adolescent rats.
    Journal of Neuroscience 10/2012; 32(43):14899-14908. · 6.75 Impact Factor
  • Source
    Acta Neuropsychiatrica 10/2012; · 0.61 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In recent years, a great deal of research has been devoted to identify new natural sources of phytosterols and to improve methods for their recovery and purification. In this regard, unexplored natural sources of bioactive ingredients are gaining much attention since they can lead to the isolation of new compounds or bioactivities. The field of available natural sources has been further increased by including algae and, even more interestingly, microalgae. In the present study, a multidisciplinary approach has been used considering, in an integrated view, extraction, chemical composition and bioactivity of phytosterols from the microalga Dunaliella tertiolecta. A novel methodology to extract, separate and characterize microalgal-derived phytosterols has been developed. In addition, recoverable and reusable eluents have been selected in order to reduce the quantities of employed organic solvents. Finally, we addressed the question whether orally administered phytosterols reach the brain and if those interfere with the major neurotransmitter systems, such as the dopaminergic, serotoninergic and noradrenergic ones, in several brain areas of rats. Flash Liquid Chromatography has been used to separate the Total Sterol (TS) fraction, composed of twelve sterols, with a purity of 97.87% and a recovery percentage of 98%, while the "flash version" of Silver Ion Liquid Chromatography has been used to purify the most abundant phytosterols in TS, (22E,24R)- methylcholesta-5,7,22-trien-3β-ol (ergosterol) and (22E,24R)-ethylcholesta-5,7,22-trien-3β-ol (7-dehydroporiferasterol), with a purity of 97.4%. These two combined methods did not need sophisticated technologies but only cheap laboratory supplies. Moreover, the possibility of recovering and recycling the solvents used as eluents made it a cleaner process. Finally, for the first time, a neuromodulatory action of Dunaliella tertiolecta-derived phytosterols has been found in selective brain areas of rats.
    Current Medicinal Chemistry 04/2012; 19(18):3058-67. · 3.72 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Oxidative stress is thought to be involved in the development of behavioral and histopathological alterations in animal models of psychosis. Here we investigate the causal contribution of reactive oxygen species generation by the phagocyte NADPH oxidase NOX2 to neuropathological alterations in a rat model of chronic psychosocial stress. In rats exposed to social isolation, the earliest neuropathological alterations were signs of oxidative stress and appearance of NOX2. Alterations in behavior, increase in glutamate levels and loss of parvalbumin were detectable after 4 weeks of social isolation. The expression of the NOX2 subunit p47(phox) was markedly increased in pyramidal neurons of isolated rats, but below detection threshold in GABAergic neurons, astrocytes and microglia. Rats with a loss of function mutation in the NOX2 subunit p47(phox) were protected from behavioral and neuropathological alterations induced by social isolation. To test reversibility, we applied the antioxidant/NOX inhibitor apocynin after initiation of social isolation for a time period of 3 weeks. Apocynin reversed behavioral alterations fully when applied after 4 weeks of social isolation, but only partially after 7 weeks. Our results demonstrate that social isolation induces rapid elevations of the NOX2 complex in the brain. Expression of the enzyme complex was strongest in pyramidal neurons and a loss of function mutation prevented neuropathology induced by social isolation. Finally, at least at early stages, pharmacological targeting of NOX2 activity might reverse behavioral alterations.
    Translational psychiatry. 02/2012; 2:e111.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: THE ENDOCANNABINOID SYSTEM SHOWS FUNCTIONAL ACTIVITY FROM EARLY STAGES OF BRAIN DEVELOPMENT: it plays an important role in fundamental developmental processes such as cell proliferation, migration, and differentiation, thus shaping brain organization during pre- and postnatal life. Cannabis sativa preparations are among the illicit drugs most commonly used by young people, including pregnant women. The developing brain can be therefore exposed to cannabis preparations during two critical periods: first, in offspring of cannabis-using mothers through perinatal and/or prenatal exposure; second, in adolescent cannabis users during neural maturation. In the last decade, it has become clear that the endocannabinoid system critically modulates memory processing and emotional responses. Therefore, it is well possible that developmental exposure to cannabinoid compounds induces enduring changes in behaviors and neural processes belonging to the cognitive and emotional domains. We address this issue by focusing on rodent studies, in order to provide a framework for understanding the impact of cannabinoid exposure on the developing brain.
    Frontiers in Behavioral Neuroscience 01/2012; 6:2. · 4.16 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cannabinoid compounds may influence both emotional and cognitive processes depending on the level of environmental aversiveness at the time of drug administration. However, the mechanisms responsible for these responses remain to be elucidated. The present experiments investigated the effects induced by the endocannabinoid transport inhibitor AM404 (0.5-5 mg/kg, i.p.) on both emotional and cognitive performances of rats tested in a Spatial Open Field task and subjected to different experimental settings, named High Arousal (HA) and Low Arousal (LA) conditions. The two different experimental conditions influenced emotional reactivity independently of drug administration. Indeed, vehicle-treated rats exposed to the LA condition spent more time in the center of the arena than vehicle-treated rats exposed to the HA context. Conversely, the different arousal conditions did not affect the cognitive performances of vehicle-treated animals such as the capability to discriminate a spatial displacement of the objects or an object substitution. AM404 administration did not alter locomotor activity or emotional behavior of animals exposed to both environmental conditions. Interestingly, AM404 administration influenced the cognitive parameters depending on the level of emotional arousal: it impaired the capability of rats exposed to the HA condition to recognize a novel object while it did not induce any impairing effect in rats exposed to the LA condition. These findings suggest that drugs enhancing endocannabinoid signaling induce different effects on recognition memory performance depending on the level of emotional arousal induced by the environmental conditions.
    Frontiers in Behavioral Neuroscience 01/2012; 6:11. · 4.16 Impact Factor
  • Source
    CURRENT MEDICINAL CHEMISTRY. 01/2012;

Publication Stats

4k Citations
731.78 Total Impact Points

Institutions

  • 2013–2014
    • The American University of Rome
      Roma, Latium, Italy
  • 2002–2014
    • Sapienza University of Rome
      • Department of Physiology and Pharmacology "Vittorio Erspamer"
      Roma, Latium, Italy
  • 2004–2013
    • Università degli studi di Foggia
      • Department of Biomedical Science
      Foggia, Apulia, Italy
  • 2012
    • Università Degli Studi Roma Tre
      • Department of Biology
      Roma, Latium, Italy
  • 2003–2009
    • University of California, Irvine
      • • Pharmacology
      • • Department of Psychiatry & Human Behavior
      Irvine, CA, United States
    • Università degli studi di Cagliari
      • Department of Environmental and Life Science
      Cagliari, Sardinia, Italy
  • 2008
    • Albert Einstein College of Medicine
      • Diabetes Research Center
      New York City, NY, United States
  • 2001–2008
    • Universita degli studi di Ferrara
      • Section of Pharmacology
      Ferrara, Emilia-Romagna, Italy
  • 1981–2008
    • Università degli Studi di Bari Aldo Moro
      • Dipartimento di Scienze Biomediche ed Oncologia Umana (DIMO)
      Bari, Apulia, Italy
  • 2007
    • Università Politecnica delle Marche
      Ancona, The Marches, Italy
    • Università degli Studi di Sassari
      Sassari, Sardinia, Italy
  • 2006
    • McGill University
      • Department of Psychiatry
      Montréal, Quebec, Canada
  • 2000
    • Università degli Studi di Palermo
      Palermo, Sicily, Italy
  • 1981–1997
    • University of Milan
      • • Department of Pharmacological Sciences
      • • Center of Neuropharmacology
      Milano, Lombardy, Italy
  • 1988–1993
    • Istituto Superiore di Sanità
      • Department of Cell Biology and Neuroscience
      Roma, Latium, Italy
    • Johns Hopkins University
      • Department of Environmental Health Sciences
      Baltimore, MD, United States
  • 1986
    • King's College London
      Londinium, England, United Kingdom