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ABSTRACT: Altered regulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with stress-induced changes in cognitive, emotional, and physical health. Recent evidence indicates that the endogenous cannabinoid (eCB) system may modulate HPA-axis function both directly and more centrally, via regulation of limbic brain systems that control HPA-axis activity. The current study examines the contribution of cannabinoid type 1 (CB1) receptor modulation throughout the neuraxis on control and stress-induced HPA-axis activity. Adult male Sprague-Dawley rats were given intraperitoneal injections of either CB1 receptor antagonist (AM251, 2 mg/kg) or vehicle 30 min prior to a session of loud white noise stress (95 dBA for 30 min) or placement in a familiar sound-proof chamber. Immediately following stress and control treatments, rats were killed, the brains and pituitary glands were excised for subsequent immediate early gene (c-fos mRNA) measurement, and trunk blood was collected for subsequent determination of corticosterone (CORT) and adrenocorticotropic (ACTH) hormone levels. AM251 treatment resulted in a potentiated plasma ACTH response to loud noise stress. AM251 treatment also increased stress-induced plasma CORT levels, but that increase may be due to an increase in basal plasma CORT levels, as was evident in control rats. AM251 treatment produced three distinctive c-fos mRNA response patterns across the various brain regions examined. In cortical (prelimbic, infralimbic, somatosensory, and auditory) and some subcortical structures (basolateral amygdala and paraventricular nucleus of the hypothalamus), AM251 treatment produced a substantial increase in c-fos mRNA that was comparable with the elevated c-fos mRNA levels present in those brain regions of both vehicle and AM251-treated stressed rats. In some other subcortical structures (bed nucleus of the stria terminalis and medial preoptic area) and the anterior pituitary, AM251 treatment produced a c-fos mRNA response pattern that was similar to the response pattern of ACTH hormone levels, that is, no effect on no noise control levels, but an augmentation of stress-induced levels. Conversely, in the medial geniculate and ventral posterior thalamus, AM251 treatment inhibited stress-induced c-fos mRNA induction. These data indicate that disruption of eCB signaling through CB1 receptors results in potentiated neural and endocrine responses to loud noise stress, but also substantial increases in activity in various brain regions and the adrenal gland.
Neuroscience 11/2011; 204:64-73. · 3.38 Impact Factor
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ABSTRACT: Neurotrophic factors, including basic fibroblast growth factor (FGF-2) and brain-derived neurotrophic factor (BDNF) are known to be affected by exposure to stressful experiences. Here, we examine the effects of behaviorally controllable (escapable tailshock, ES) or uncontrollable (inescapable tailshock, IS) stress on the expression of FGF-2 and BDNF mRNA in subregions of the medial prefrontal cortex (mPFC) and the hippocampal formation (HF) of male Sprague-Dawley rats. ES rats were placed in Plexiglas boxes equipped with a free spinning wheel and IS rats were placed in identical boxes with the wheels fixed. ES and IS rats were yoked such that they received the same tailshocks, but the ES rat could terminate each shock for both rats. No stress controls (NS) remained in their home cages. Rats were killed 0, 2, 24, or 72 h after termination of the stress session. In situ hybridization was performed to measure FGF-2 and BDNF mRNA in the mPFC and HF. In the mPFC, ES produced a significant increase in FGF-2 mRNA expression at 0 and 2 h post-stress. In the HF, ES produced a greater increase in FGF-2 mRNA expression than IS and NS only in CA2. ES also produced an increase in BDNF mRNA expression in the anterior cingulate at 0 h post-stress. No effects of stressor controllability on BDNF were observed in the HF, although both ES and IS decreased BDNF mRNA in the DG. FGF-2 in the mPFC may be involved in emotional regulation ("coping") during stressful experiences.
Neuroscience 03/2007; 144(4):1219-28. · 3.38 Impact Factor
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ABSTRACT: Corticosterone regulates both basal and stress-induced hypothalamic-pituitary-adrenal (HPA) axis activity in a negative-feedback fashion. However, the cellular and molecular mechanisms of this negative feedback have yet to be explicitly characterized. By comparing stress-induced c-fos and corticotropin-releasing hormone (CRH) expression in the paraventricular nucleus (PVN), we may be able to determine whether acute glucocorticoid treatment affects the net neural excitatory input to the PVN (represented primarily by c-fos mRNA expression) or directly affects the ability of cells in the PVN to respond to that input (represented primarily by CRH hnRNA expression). In the following studies, we observed the effect of acute glucocorticoid (RU28362) treatment on subsequent HPA axis reactivity by measuring stress-induced plasma hormone concentration [corticosterone and adrenocorticotropic hormone (ACTH)] and gene expression (c-fos and CRH) in the PVN. First, we examined the dose-response relationship between systemically administered RU28362 (1-150 microg/kg, i.p) and suppression of the stress-induced corticosterone response. We then confirmed central nervous system access of the maximally suppressive dose of RU28362 (150 microg/kg) by an ex vivo radioligand binding assay. RU28362 selectively occupied the majority of glucocorticoid receptors in the hippocampus and hypothalamus while having no effect on mineralocorticoid receptors. In separate studies, RU28362 (150 microg/kg) and corticosterone (5 mg/kg) were injected i.p. 1 h before restraint stress. Compared to vehicle-treated controls, rats treated with RU28362 and corticosterone had substantially blunted stress-induced corticosterone and ACTH production, respectively. Furthermore, treatment with RU28362 significantly blunted stress-induced CRH hnRNA expression in the PVN. By contrast, neither RU28362 nor corticosterone treatment had an effect on stress-induced neuronal activation as measured by c-fos mRNA and its protein product in the PVN. This dissociation between c-fos and CRH gene expression suggests that glucocorticoid suppression of HPA activity within this time-frame is not a result of decreased excitatory neural input to the PVN, but instead depends on some direct effect of RU28362 on cells intrinsic to the HPA axis.
Journal of Neuroendocrinology 12/2003; 15(11):1075-83. · 3.14 Impact Factor
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ABSTRACT: We reported previously that environmental novelty enhances the acute psychomotor activating effects of amphetamine, its ability to induce behavioral sensitization, and its ability to induce c-fos mRNA in the striatum and other structures, relative to when amphetamine is given in the home cage. The purpose of the present experiment was 2-fold: to determine (1) whether environmental novelty has a similar effect on the ability of cocaine to induce c-fos mRNA, and (2) whether this effect is seen in neurologically-intact rats (in previous experiments we studied the intact hemisphere of rats with a unilateral 6-OHDA lesion). In the dorsal portion of the caudate putamen, core and shell of the nucleus accumbens, and in several cortical regions, both amphetamine (1.5 mg/kg) and cocaine (15 mg/kg) induced higher levels of c-fos mRNA expression when administered in a novel environment, relative to when they were administered in the home cage. The ability of environmental context to modulate psychostimulant drug-induced immediate early gene expression may be related to its ability to modulate forms of drug experience-dependent plasticity, such as behavioral sensitization.
Brain Research 12/2001; 920(1-2):106-16. · 2.73 Impact Factor
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ABSTRACT: In the dorsal striatum, there are two major populations of medium spiny projection neurons. One population is positive for dynorphin mRNA (DYN+), and these cells project preferentially to the substantia nigra, forming the so-called 'direct pathway'. A second population is positive for enkephalin mRNA (ENK+), and these cells influence the substantia nigra indirectly, via the globus pallidus and subthalamic nucleus. Psychostimulant drugs, such as amphetamine and cocaine, are reported to induce immediate early genes (IEGs) in only one subpopulation of dorsal striatal projection neurons, DYN+ cells. However, this apparent selectivity appears to be a function of environmental context. We found that when given in the animal's home cage, amphetamine and cocaine increased expression of the IEG, c-fos, almost exclusively in DYN+ cells. However, when given in a novel environment, amphetamine and cocaine increased c-fos mRNA in both DYN+ and ENK+ cells. Furthermore, amphetamine and cocaine increased c-fos mRNA expression in the subthalamic nucleus when administered in the novel environment, but not when given at home. We conclude that the neural circuitry engaged by psychostimulant drugs, and their ability to induce specific patterns of gene expression, are determined by the environmental context in which they are experienced. This may be related to the ability of environmental novelty to facilitate psychostimulant drug-induced neuroplasticity.
European Journal of Neuroscience 06/2001; 13(10):1977-83. · 3.63 Impact Factor
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ABSTRACT: The environmental context in which amphetamine or cocaine are administered modulates both their acute psychomotor activating effects and their ability to induce sensitization. Here we report that environmental context differentially affects patterns of amphetamine- and cocaine-induced c-fos mRNA expression in the bed nucleus of the stria terminalis (BST) and amygdala of male rats. In the medial amygdala and medial posterior BST, exposure to novelty resulted in a marked increase in c-fos mRNA. Amphetamine given at home did not induce c-fos mRNA, and when given in the novel environment, did not increase levels beyond that observed for novelty alone. In the basolateral and lateral amygdala, amphetamine or cocaine at home or exposure to novelty induced c-fos mRNA. When amphetamine or cocaine was given in a novel environment the c-fos mRNA response was significantly enhanced. In the central nucleus of the amygdala (CEA) and oval subnucleus of the BST (BSTov), amphetamine administration at home produced a robust increase in c-fos mRNA expression, whereas exposure to novelty had little effect. In contrast to other brain regions examined, the c-fos mRNA response to amphetamine in a novel versus home environment was significantly smaller. In both "home" and "novel" amphetamine groups, c-fos mRNA in the BSTov and CEA was predominantly expressed in enkephalin-containing cells; coexpression with corticotropin-releasing hormone was rare. These data suggest that the context in which psychostimulants are given powerfully and differentially alters the response of limbic structures that have been functionally implicated in drug reinforcement and emotional behaviors.
Journal of Neuroscience 02/2001; 21(2):732-40. · 7.11 Impact Factor
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ABSTRACT: Considerable evidence supports a role for brainstem adrenergic and noradrenergic inputs to corticotropin-releasing hormone (CRH) cells of the hypothalamic paraventricular nucleus (PVN), in the control of hypothalamic-pituitary-adrenocortical (HPA) axis function. However, little is known about specific adrenoceptor (ADR) subtypes in CRH-containing cells of the PVN. Here we demonstrate, using dual in situ hybridization, that mRNA encoding alpha(1b) ADR is colocalized with CRH in the rat PVN. Furthermore, we confirm that these alpha(1b) ADR mRNA-containing cells are stress-responsive, by colocalization with c-fos mRNA after restraint, swim, or immune stress. To determine whether expression of alpha(1b) ADR mRNA is influenced by circulating glucocorticoids, male rats underwent bilateral adrenalectomy (ADX) or sham surgery, and were killed after 1, 3, 7, or 14 d. In situ hybridization revealed levels of alpha(1b) ADR mRNA were increased in the PVN 7 and 14 d after ADX, but were not altered in the hippocampus, amygdala, or dorsal raphe. Additional rats underwent ADX or sham surgery and received a corticosterone pellet (10 or 50 mg) or placebo for 7 d. Corticosterone replacement (10 mg) reduced the ADX-induced increase in PVN alpha(1b) ADR mRNA to control levels, whereas 50 mg of corticosterone replacement resulted in a decrease in PVN alpha(1b) ADR mRNA as compared with all other groups. Furthermore, levels of plasma corticosterone were significantly correlated (inverse relationship) with alpha(1b) ADR mRNA in the PVN. We conclude that alpha(1b) ADR mRNA is expressed in CRH-containing, stress-responsive cells of the PVN and is highly sensitive to circulating levels of corticosterone. Because activation of the alpha(1B) adrenoceptor is predominantly excitatory within the brain, we predict that this receptor plays an important role in facilitation of the HPA axis response.
Journal of Neuroscience 12/1999; 19(22):10098-106. · 7.11 Impact Factor
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ABSTRACT: The lateral division of the central nucleus of the amygdala (CEAl) and the oval nucleus of the bed nucleus of the stria terminalis (BSTov) have been linked closely anatomically and functionally. To determine whether these regions may be subdivided further on a neurochemical basis, dual in situ hybridization was used to determine the colocalization of corticotropin-releasing hormone (CRH), enkephalin (ENK), or neurotensin (NT) with glutamic acid decarboxylase isoforms 65 and 67 [used concurrently as a marker for gamma-aminobutyric acid GABA] in these nuclei. It was found that, for both regions, each peptide invariably was localized in a GABAergic cell. Although there was a similar overlap in the distribution of NT with ENK in the BSTov and CEAl, it was observed that CRH and ENK rarely were colocalized in either nucleus. To determine whether these distinct neuronal populations could be activated differentially, male rats were given a systemic injection of interleukin-1beta (IL-1beta; 5 microg/kg, i.p.), a stimulus that results in a robust increase in c-fos mRNA expression in the BSTov and CEAl. The neurochemical identity of these activated neurons showed striking similarities between the BSTov and the CEAl; All IL-1beta-responsive cells were GABAergic, the majority of c-fos- positive cells expressed ENK mRNA (BSTov, 81%; CEAl, 94%), and some expressed NT mRNA (BSTov, 23%; CEAl, 22%), whereas very few expressed CRH mRNA (BSTov, 4%; CEAl, 1%). These data provide evidence for the existence of discrete neural circuits within the BSTov and CEAl, and the similarities in the patterns of neurochemical colocalization in these nuclei are consistent with the concept of an extended amygdala. Furthermore, these data indicate that intraperitoneal IL-1beta recruits neurochemically distinct pathways within the BSTov and CEAl, and it is suggested that this differential activation may mediate specific aspects of immune, limbic, and/or autonomic processes.
The Journal of Comparative Neurology 11/1999; 413(1):113-28. · 3.81 Impact Factor
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ABSTRACT: We have reported previously that exposure to environmental novelty enhances the behavioral activating effects of amphetamine and its ability to induce the immediate early gene c-fos in the striatum and in other brain regions. In the present study, we used double in situ hybridization histochemistry to study the effect of amphetamine and/or novelty on c-fos expression in two populations of striatal neurons that preferentially express either D1 or D2 dopamine receptor mRNA. When given intraperitoneally to rats in their home cage, amphetamine (2.0 mg/kg) increased c-fos expression only in D1 neurons. In contrast, when the same dose of amphetamine was administered to rats in a novel environment, c-fos was increased in both D1 and D2 neurons. We conclude that the neural populations engaged by amphetamine vary as a function of the circumstances surrounding its administration.
Behavioural Brain Research 10/1999; 103(2):203-9. · 3.42 Impact Factor
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ABSTRACT: Agouti-related protein (AGRP) is a recently discovered orexigenic neuropeptide that inhibits the binding and action of alpha-melanocyte-stimulating hormone derived from proopiomelanocortin (POMC) at the melanocortin 3 receptor (MC3R) and melanocortin 4 receptor (MC4R) and has been proposed to function primarily as an endogenous melanocortin antagonist. To better understand the interplay between the AGRP and melanocortin signaling systems, we compared their nerve fiber distributions with each other by immunohistochemistry and their perikarya distribution with MC3R and MC4R by double in situ hybridization. Although deriving from distinct cell groups, AGRP and melanocortin terminals project to identical brain areas. Both AGRP and melanocortin neurons selectively express the MC3R, which provides a neuroanatomical basis for a dual-input circuit with biological amplification and feedback inhibition. These studies highlight a broader complexity in POMC-mediated behavior in the brain.
Journal of Neuroscience 10/1999; 19(18):RC26. · 7.11 Impact Factor
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ABSTRACT: The purpose of this study was to investigate a putative role for cholecystokinin (CCK) in the activation of the hypothalamic-pituitary-adrenal (HPA) axis following intraperitoneal (i.p.) administration of interleukin-1-beta (IL-1beta). Previous studies predict that CCKA receptors on vagal sensory afferents may be involved in the initiation of the stress response following an acute i.p. injection of IL-1beta. Adult male rats were given an i.p. injection of a specific CCKA (devazepide, 1 mg/kg) or CCKB (CI-988, 1 mg/kg) receptor antagonist, 30 min prior to an i.p. injection of rat recombinant IL-1beta (rrIL-1beta), 0.5 microg/kg in 0.9% sterile saline/0.01% rat serum albumin. Blood samples were obtained via an indwelling jugular vein catheter, and the plasma levels of the stress hormones ACTH (adrenocorticotropin hormone) and corticosterone analysed over time as an indicator of HPA axis activation. This dose of rrIL-1beta resulted in a significant release of ACTH and corticosterone, peaking at 30-60 min, and returning to basal levels by 2 h. Pretreatment with either devazepide or CI-988 had no effect on the rrIL-1beta induced ACTH or corticosterone release. In contrast, the same dose of devazepide completely inhibited the ACTH and corticosterone response to i.p. CCK (octapeptide, sulphated form, CCK-8S), 5 microg/kg. It is concluded that CCK receptors are not involved in the hormonal stress response to a submaximal i.p. dose of rrIL-1beta.
Journal of Neuroendocrinology 08/1999; 11(7):561-8. · 3.14 Impact Factor
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ABSTRACT: We have shown recently that the psychomotor activating effects of amphetamine in the rat are much greater when this drug is administered in association with environmental novelty than when it is given in a home environment. The main purpose of the present study was to explore the neural basis of this phenomenon. We found, using in situ hybridization of c-fos mRNA, that the pattern of neuronal activation in the cortex, in the caudate, in the shell and core of the nucleus accumbens, and in other subcortical structures was markedly different when amphetamine (2.0 mg/kg, i.p.) was given in association with exposure to environmental novelty relative to when it was given at home. In most brain regions the magnitude of c-fos expression was over two times greater in rats given amphetamine plus novelty than in rats given amphetamine alone. In contrast, an in vivo microdialysis study indicated that environmental novelty did not affect amphetamine-induced dopamine release in either caudate or nucleus accumbens. Furthermore, a unilateral 6-hydroxydopamine lesion of the mesostriatal dopamine system reduced amphetamine- but not novelty-induced c-fos expression. Finally, we found no differences in the amount of corticosterone secreted after exposure to novelty, amphetamine, or both, suggesting that corticosterone does not play a critical role in the ability of novelty to modulate amphetamine-induced psychomotor activation. In conclusion, it seems that environmental novelty alters the neurobiological effects of amphetamine independently of the primary neuropharmacological actions of this drug in the striatum.
Journal of Neuroscience 01/1999; 18(24):10579-93. · 7.11 Impact Factor
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ABSTRACT: In recent years nitric oxide (NO) has emerged as a unique biological messenger. NO is a highly diffusible gas, synthesized from L-arginine by the enzyme nitric oxide synthase (NOS). Three unique subtypes of NOS have been described, each with a specific distribution profile in the brain and periphery. NOS subtype I is present, among other areas, in the hippocampus, hypothalamus, pituitary and adrenal gland. Together these structures form the limbic-hypothalamic-pituitary-adrenal (LHPA) or stress axis, activation of which is one of the defining features of a stress response. Evidence suggests that NO may modulate the release of the stress hormones ACTH and corticosterone, and NOS activity and transcription is increased in the LHPA axis following various stressful stimuli. Furthermore, following activation of the stress axis, glucocorticoids are thought to down-regulate the transcription and activity of NOS via a feedback mechanism. Taken together, current data indicate a role for NO in the regulation of the LHPA axis, although at present this role is not well defined. It has been suggested that NO may act as a cellular communicator in plasticity and development, to facilitate the activation or the release of other neurotransmitters, to mediate immune responses, and/or as a vasodilator in the regulation of blood flow. In the following review we summarize some of the latest insights into the function of NO, with special attention to its relationship with the LHPA axis.
Histology and histopathology 11/1998; 13(4):1243-52. · 2.48 Impact Factor
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ABSTRACT: The goal of this article is to describe some of the central nervous system circuits involved in the regulation of the hypothalamopituitary-adrenocortical (HPA) axis, with an emphasis on animal models believed to mimic the human experience of emotional stress. First, the basic constitutive elements of the HPA axis that control glucocorticoid secretion are reviewed. A description of the neural systems assumed to regulate the activity of the HPA axis, both anatomically and functionally, follows. It is argued that hypothalamic, septal and bed nucleus of the stria terminalis neurons are involved in the regulation of the HPA axis by situations eliciting emotional responses.
Psychiatric Clinics of North America 07/1998; 21(2):259-76. · 2.13 Impact Factor
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ABSTRACT: The technique of in situ hybridization with specific ribonucleotide probes was used to determine the distribution patterns of mRNA encoding the alpha 1a-, alpha 1b- and alpha 1d-adrenoceptor (AR) subtypes in rat brain and spinal cord. The expression pattern of alpha 1a-AR mRNA has not been reported previously, and was found to be widespread throughout the rat central nervous system. High levels were found in regions of the olfactory system, several hypothalamic nuclei, and regions of the brainstem and spinal cord, particularly in areas related to motor function. Regions expressing moderate levels of mRNA for this receptor were the septum, bed nucleus of the stria terminalis, cerebral cortex, amygdala, cerebellum and pineal gland. Low expression levels were detected in the hippocampal formation. Most nuclei in the basal ganglia and thalamus expressed extremely low or undetectable levels of alpha 1a-AR mRNA. The expression patterns of the alpha 1b- and alpha 1d-AR mRNAs were similar to those described using oligonucleotide probes in earlier studies. High expression of alpha 1b-AR mRNA was noted in the pineal gland, most thalamic nuclei, lateral nucleus of the amygdala and dorsal and median raphe nuclei. Moderate expression levels were noted throughout the cerebral cortex, and in some olfactory, septal, and brainstem regions. The distribution of alpha 1d-AR mRNA was the most discrete of the three receptors examined. Expression was strong in the olfactory bulb, cerebral cortex, hippocampus, reticular thalamic nucleus, regions of the amygdala, motor nuclei of the brainstem, inferior olivary complex and spinal cord. Comparison of the distributions of the alpha 1a-, alpha 1b- and alpha 1d-AR mRNA suggests unique functional roles for each of these receptors.
Journal of Chemical Neuroanatomy 08/1997; 13(2):115-39. · 2.43 Impact Factor
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ABSTRACT: Interleukin-1-beta (IL-1 beta) is a potent activator of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in the release of corticosteroids from the adrenal glands. This effect is evident after both central and peripheral administration, and controversy surrounds the mechanism(s) by which systemic administration of this peptide, which should not cross the blood-brain barrier, may activate the HPA axis. In the present study, IL-1 beta was administered systemically (5 micrograms/kg i.p.) or centrally (100 ng i.c.v.) to male rats. Both routes of administration of IL-1 beta resulted in significant and comparable activation of the HPA axis, as assessed by analysis of plasma conrticosterone. In addition, both routes of administration of IL-1 beta resulted in c-fos mRNA induction in specific regions, as determined by in situ hybridization. These included the meninges, cerebral vasculature, choroid plexus and circumventricular organs. Semiquantitative analysis revealed that both routes of administration resulted in significant and comparable induction of c-fos mRNA in the paraventricular nucleus of the hypothalamus, as compared with control animals. In contrast, in the nucleus tractus solitarius (NTS) and central nucleus of the amygdala (CeA), levels of c-fos mRNA were 3-4 times higher in animals treated intraperitoneally compared with intracerebroventricularly. A similar differential activation of c-fos mRNA was observed in the lateral divisions of the parabrachial nucleus (PBN) and bed nucleus of the stria terminalis (BNST). These data indicate that following systemic administration, IL-1 beta may activate specific brain areas through mechanisms distinct from those involved following central administration. The differential magnitude of the c-fos mRNA response in the NTS, PBN, CeA and BNST is consistent with vagal activation. Physiologically, these results suggest that IL-1 beta may have differential central effects depending on its source or point of entry to the brain.
Neuroendocrinology 04/1996; 63(3):207-18. · 2.38 Impact Factor
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ABSTRACT: The effect of sulphated cholecystokinin octapeptide (CCK-8S) on immediate early gene expression in the rat CNS was investigated using the technique of in situ hybridization. A rapid and transient induction of c-fos, NGFI-A and NGFI-B (nerve growth factor-induced genes A and B) mRNA was demonstrated in the nucleus tractus solitarius (NTS), area postrema (AP), hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, and central nucleus of the amygdala, following peripheral administration of CCK-8S (1-100 micrograms/kg i.p.). In contrast, levels of c-jun, junB and junD mRNA were unaffected by the peptide. The closely related decapeptide, caerulein (50 micrograms/kg i.p.), induced the same pattern of IEG expression as CCK-8S, whereas the desulphated octapeptide, CCK-8DS (50 micrograms/kg i.p.), had no effect on levels of mRNA for any IEG studied. Expression of IEG mRNA in these areas was suppressed by bilateral subdiaphragmatic vagotomy, and by pretreatment with the selective CCKA receptor antagonist, devazepide (0.1 and 1 mg/kg i.p.). In contrast, CCK-8S induction of IEG mRNA was not blocked by pretreatment with the selective CCKB receptor antagonist, CI-988 (1 or 10 mg/kg i.p.). In addition, the selective CCKB receptor agonists, CCK-4 (50 micrograms/kg i.p.) or pentagastrin (2 mg/kg i.p.), failed to induce IEG expression in any of the areas studied. These results suggest that systemic CCK-8S primarily acts via CCKA receptors on vagal afferents to stimulate IEG mRNA expression in the rat CNS.
Neuropharmacology 07/1994; 33(6):719-27. · 4.81 Impact Factor
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ABSTRACT: Neurotrophic factors, including basic fibroblast growth factor (FGF-2) and brain-derived neurotrophic factor (BDNF) are known to be affected by exposure to stressful experiences. Here, we examine the effects of behaviorally controllable (escapable tailshock, ES) or uncontrollable (inescapable tailshock, IS) stress on the expression of FGF-2 and BDNF mRNA in subregions of the medial prefrontal cortex (mPFC) and the hippocampal formation (HF) of male Sprague–Dawley rats. ES rats were placed in Plexiglas boxes equipped with a free spinning wheel and IS rats were placed in identical boxes with the wheels fixed. ES and IS rats were yoked such that they received the same tailshocks, but the ES rat could terminate each shock for both rats. No stress controls (NS) remained in their home cages. Rats were killed 0, 2, 24, or 72 h after termination of the stress session. In situ hybridization was performed to measure FGF-2 and BDNF mRNA in the mPFC and HF. In the mPFC, ES produced a significant increase in FGF-2 mRNA expression at 0 and 2 h post-stress. In the HF, ES produced a greater increase in FGF-2 mRNA expression than IS and NS only in CA2. ES also produced an increase in BDNF mRNA expression in the anterior cingulate at 0 h post-stress. No effects of stressor controllability on BDNF were observed in the HF, although both ES and IS decreased BDNF mRNA in the DG. FGF-2 in the mPFC may be involved in emotional regulation (“coping”) during stressful experiences.
Neuroscience.
