Miguel Miguéns

Hospital Regional Universitario Carlos Haya Málaga, Málaga, Andalusia, Spain

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Publications (27)106.73 Total impact

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    ABSTRACT: The Lewis (LEW) and Fischer 344 (F344) rat strains have been proposed as a model to study certain genetic influences on drug use. These strains differ in terms of the self-administration of several drugs, and in their expression of various components of the dopaminergic, glutamatergic, GABAergic and endogenous opioid neurotransmitter systems. As the endocannabinoid system is linked to these systems, we investigated whether these two strains exhibit differences in cannabinoid receptor binding and in the expression of cannabinoid-related genes. Quantitative autoradiography of [(3)H]-CP 55,940 binding levels and real-time PCR assays were used. F344 rats displayed higher levels of cannabinoid receptor binding in the lateral globus pallidus and weaker CNR1 gene expression in the prefrontal cortex (PFc) than LEW rats. Moreover, the N-acyl phosphatidylethanolamine-specific phospholipase D/fatty acid amide hydrolase ratio was greater in the PFc and NAcc of F344 rats. Our results suggest that the endocannabinoid system may be a mediator of the individual differences that exist in the susceptibility to the rewarding effects of drugs of abuse.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 03/2014; · 3.55 Impact Factor
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    ABSTRACT: The Lewis (LEW) and Fischer 344 (F344) rat strains have been proposed as a model to study certain genetic influences on drug use. These strains differ in terms of the self-administration of several drugs, and in their expression of various components of the dopaminergic, glutamatergic, GABAergic and endogenous opioid neurotransmitter systems. As the endocannabinoid system is linked to these systems, we investigated whether these two strains exhibit differences in cannabinoid receptor binding and in the expression of cannabinoid-related genes. Quantitative autoradiography of [3H]-CP 55,940 binding levels and real-time PCR assays were used. F344 rats displayed higher levels of cannabinoid receptor binding in the lateral globus pallidus and weaker CNR1 gene expression in the prefrontal cortex (PFc) than LEW rats. Moreover, the N-acyl phosphatidylethanolamine-specific phospholipase D/fatty acid amide hydrolase ratio was greater in the PFc and NAcc of F344 rats. Our results suggest that the endocannabinoid system may be a mediator of the individual differences that exist in the susceptibility to the rewarding effects of drugs of abuse.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 01/2014; · 3.55 Impact Factor
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    ABSTRACT: Cocaine addiction alters synaptic plasticity in many brain areas involved in learning and memory processes, including the hippocampus. Long-term potentiation (LTP) is one of the best studied examples of hippocampal synaptic plasticity and it is considered as one of the molecular basis of learning and memory. We previously demonstrated that in the presence of cocaine, a long lasting form of hippocampal LTP is induced by a single pulse of high frequency stimulation, which in normal conditions evokes only an early form of LTP. In this study, we further explore the molecular basis of this modulation of synaptic plasticity by cocaine. By performing pharmacological experiments on hippocampal slices, we were able to show that cocaine converts early LTP to a form of LTP dependent on protein synthesis, probably through the cAMP-dependent protein kinase and extracellular signal-regulated kinase signaling cascades. We also found that metabotropic glutamate receptors are involved in this phenomenon. These studies further clarify the molecular machinery used by cocaine to alter synaptic plasticity and modulate learning and memory processes.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 11/2013; · 3.68 Impact Factor
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    ABSTRACT: Chronic exposure to cocaine induces modifications to neurons in the brain regions involved in addiction. Hence, we evaluated cocaine-induced changes in the hippocampal CA1 field in Fischer 344 (F344) and Lewis (LEW) rats, 2 strains that have been widely used to study genetic predisposition to drug addiction, by combining intracellular Lucifer yellow injection with confocal microscopy reconstruction of labeled neurons. Specifically, we examined the effects of cocaine self-administration on the structure, size, and branching complexity of the apical dendrites of CA1 pyramidal neurons. In addition, we quantified spine density in the collaterals of the apical dendritic arbors of these neurons. We found differences between these strains in several morphological parameters. For example, CA1 apical dendrites were more branched and complex in LEW than in F344 rats, while the spine density in the collateral dendrites of the apical dendritic arbors was greater in F344 rats. Interestingly, cocaine self-administration in LEW rats augmented the spine density, an effect that was not observed in the F344 strain. These results reveal significant structural differences in CA1 pyramidal cells between these strains and indicate that cocaine self-administration has a distinct effect on neuron morphology in the hippocampus of rats with different genetic backgrounds.
    Cerebral Cortex 08/2013; · 6.83 Impact Factor
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    ABSTRACT: The endocannabinoids anandamide and 2-arachidonyl glycerol (2-AG) are modulators of glutamate and γ-aminobutyric acid (GABA), two transmitters involved in cocaine addiction. However, little is known on the effects of cocaine on the enzymes that produce and degrade endocannabinoids. The present work addresses the effects of cocaine self-administration on the immunohistochemical expression of endocannabinoid signalling (ECS)-related proteins in the hippocampus. The study has been performed on two different strains of rats, Lewis (Lew) and Fischer 344 (F344), which are characterized for displaying a differential sensitivity to cocaine, thus making them suitable in the study of vulnerability to drug addiction. Both strains showed differences in the expression of ECS-related proteins in the hippocampus, i.e. Lew rats exhibited lower CB1 expression but higher CB2 expression than F344 rats. After setting similar cocaine self-administration, both strains showed clear differences in the expression of ECS-related proteins, which were differentially restricted to either the 2-AG or anandamide signalling pathways in a self-administration training/drug-dependent manner. The decreases observed in CB1 expression and N-acyl phosphatidylethanolamine phospholipase D:fatty acid amino hydrolase ratio after saline self-administration were enhanced only in cocaine self-administered Lew rats. CB2 expression increase and diacylglycerol lipase α:monoacylglycerol lipase ratio decrease detected after saline self-administration were blocked only in cocaine self-administered F344 rats. These findings indicate that cocaine may regulate hippocampal GABA/glutamate synapses by directly modulating endocannabinoid production/degradation enzymes and that these actions are strain-dependent. This differential response suggests that the endogenous cannabinoid system might contribute to genotype/strain differences on the sensitivity to self-administration training and cocaine addiction.
    The International Journal of Neuropsychopharmacology 12/2012; · 5.64 Impact Factor
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    ABSTRACT: Adolescence is a period of active synaptic remodelling and plasticity and as such, a developmental phase of particular vulnerability to the effects of environmental insults. The endogenous cannabinoid system regulates central nervous system development and cannabinoid exposure during adolescence has been linked to several alterations to hippocampal-dependent processes such as cognition and emotion, which rely on intact glutamatergic and GABAergic systems. Here we show that K(+)-induced γ-amino butyric acid (GABA) release increases in the CA1 hippocampal field of Wistar rats of both sexes that were treated chronically with the cannabinoid agonist CP 55,940 (CP55940) during adolescence. GABA(B) receptors levels also increased in cannabinoid-exposed rats. In addition, CP55940-treated females exhibit reduced GABA transporter gene expression (GAT-1), increased GABA(A) receptor expression, as well as decreased K(+)-induced glutamate release and NMDA receptor levels. CP55940 administration did not affect the glial (EAAT2) or neuronal (EAAT3) glutamate transporter gene expression in either males or females, and nor were any changes in the mGlu5 receptor protein levels observed. Taken together, these results show that while the exacerbated GABA release induced by early cannabinoid exposure may be compensated by an increment in GABA(B) receptors, which normally function as inhibitory autoreceptors, adolescent cannabinoid exposure in the females disturbs the normal balance between glutamate and GABA transmission. These observations may provide important insight into the neuronal basis of the well-documented alterations in cognitive and emotional processes induced by adolescent cannabinoid exposure.
    Neuropharmacology 04/2012; 62(5-6):1975-84. · 4.11 Impact Factor
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    ABSTRACT: The Lewis (LEW) and Fischer 344 (F344) inbred rat strains are frequently used to study the role of genetic factors in vulnerability to drug addiction and relapse. Glutamate and γ-amino butyric acid (GABA) transmission are significantly altered after cocaine-induced reinstatement, although whether LEW and F344 rats differ in their accumbal glutamate and GABA responsiveness to cocaine-induced reinstatement remains unknown. To investigate this, we measured by in vivo microdialysis extracellular glutamate and GABA levels in the core division of the nucleus accumbens after extinction of cocaine self-administration and during cocaine-induced reinstatement (7.5 mg/kg, i.p.) in these two strains of rats. No strain differences were evident in cocaine self-administration or extinction behavior, although cocaine priming did induce a higher rate of lever pressing in LEW compared with F344 rats. After extinction, F344 rats that self-administered cocaine had less GABA than the saline controls, while the glutamate levels remained constant in both strains. There was more accumbal glutamate after cocaine priming in LEW rats that self-administered cocaine, while GABA levels were unaffected. By contrast, GABA increased transiently in F344 rats that self-administered cocaine, while glutamate levels were unaltered. In F344 saline controls, cocaine priming provoked contrasting effects in glutamate and GABA levels, inducing a delayed increase in glutamate and a delayed decrease in GABA levels. These amino acids were unaffected by cocaine priming in LEW saline rats. Together, these results suggest that genetic differences in cocaine-induced reinstatement reflect different responses of the accumbal GABA and glutamate systems to cocaine priming.
    Addiction Biology 10/2011; · 5.91 Impact Factor
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    ABSTRACT: Lewis (LEW) and Fischer 344 (F344) rats differ in their response to drugs and are frequently used as an experimental model to study vulnerability to drug addiction. We have previously reported that significant differences in hippocampal synaptic plasticity exist between LEW and F344 rats after non-contingent chronic cocaine administration. However, given the several biochemical differences between contingent and non-contingent administration of drugs, we have studied here the possible genetic differences in synaptic plasticity after contingent cocaine self-administration. LEW and F344 animals self-administered cocaine (1 mg/kg i.v.) or saline under a fixed ratio 1 schedule of reinforcement for 20 days. After self-administration, electrophysiological experiments were carried out in which hippocampal slices were tetanized with three high frequency pulses in order to induce long-term potentiation (LTP). After a 20 min period of LTP stabilization, a train of low frequency stimulation (LFS; 900 pulses, 1 Hz) was applied to induce depotentiation of LTP. Data showed no differences between cocaine self-administered LEW or F344 rats in the induction of saturated-LTP compared to saline animals. LEW saline self-administered rats showed normal LTP depotentiation whereas cocaine self-administration impaired depotentiation in this rat strain. In the F344 strain, depotentiation of saturated-LTP was impaired both in saline and cocaine self-administered rats. The present results corroborate previous findings showing differences in basal hippocampal synaptic plasticity between LEW and F344 rats. These differences seem to modulate cocaine effects in a manner independent of contingency of drug administration.
    Neuroscience 07/2011; 187:36-42. · 3.12 Impact Factor
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    ABSTRACT: Dose-response studies are thought to be a valuable tool to predict the most genetically drug-vulnerable individuals. However, dose-response curves for morphine self-administration have not yet been examined and nor strain differences might be evident. Therefore, this study aimed to define the dose-response curve for morphine self-administration (0.25, 0.5, 1 and 2 mg/kg) in Lewis (LEW) rats and their histocompatible Fischer-344 (F344) rats. In addition, impulsivity has been suggested as one of the genetic factors contributing most to the initiation of drug use. Therefore, the impulsive choice of both rat strains in the presence or absence of the same morphine doses was also analysed. LEW rats self-administered significantly more morphine whatever the dose tested and they exhibited greater basal impulsive choice compared with F344 rats. The F344 strain showed a preference for the dose of 0.5 mg/kg, while any of the doses used had a differential reinforcing effect in the LEW strain. The basal pattern of strain differences in impulsive choice was not affected by morphine administration. These data suggest that the LEW strain has a highly drug-vulnerable phenotype and they point to the strength of impulsivity as a pre-existing behavioural trait that might make this rat strain more vulnerable to the reinforcing effects of drugs and, therefore, to develop addiction.
    Journal of Psychopharmacology 06/2011; 25(6):783-91. · 3.37 Impact Factor
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    ABSTRACT: Drug addiction results from the interplay between social and biological factors. Among these, genetic variables play a major role. The use of genetically related inbred rat strains that differ in their preference for drugs of abuse is one approach of great importance to explore genetic determinants. Lewis and Fischer 344 rats have been extensively studied and it has been shown that the Lewis strain is especially vulnerable to the addictive properties of several drugs when compared with the Fischer 344 strain. Here, we have used microarrays to analyze gene expression profiles in the frontal cortex and nucleus accumbens of Lewis and Fischer 344 rats. Our results show that only a very limited group of genes were differentially expressed in Lewis rats when compared with the Fischer 344 strain. The genes that were induced in the Lewis strain were related to oxygen transport, neurotransmitter processing and fatty acid metabolism. On the contrary genes that were repressed in Lewis rats were involved in physiological functions such as drug and proton transport, oligodendrocyte survival and lipid catabolism.These data might be useful for the identification of genes which could be potential markers of the vulnerability to the addictive properties of drugs of abuse.
    DNA research: an international journal for rapid publication of reports on genes and genomes 03/2011; 9(1):143-50. · 1.73 Impact Factor
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    ABSTRACT: The high rate of recidivism in cocaine addiction after prolonged periods of abstinence poses a significant problem for the effective treatment of this condition. Moreover, the neurobiological basis of this relapse phenomenon remains poorly understood. In this review, we will discuss the evidence currently available regarding the neurobiological changes during the extinction of cocaine self-administration. Specifically, we will focus on alterations in the dopaminergic, opioidergic, glutamatergic, cholinergic, serotoninergic and CRF systems described in self-administration experiments and extinction studies after chronic cocaine administration. We will also discuss the differences related to contingent versus non-contingent cocaine administration, which highlights the importance of environmental cues on drug effects and extinction. The findings discussed in this review may aid the development of more effective therapeutic approaches to treat cocaine relapse.
    Pharmaceuticals 01/2011; 4:1315-1327.
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    ABSTRACT: In a previous work, we have shown that chronic administration of the cannabinoid agonist CP 55,940 (CP) during periadolescence increases cocaine self-administration in adult female rats, while it produces no such effect in males (Higuera-Matas et al., 2008). To extend these findings, we have analysed here the brains of the rats used as subjects in this previous work to evaluate the impact of the interaction between CP exposure and cocaine self-administration on dopaminergic parameters. We evaluated the levels of the dopamine transporter (DAT), and the D1- (D1R) and D2-type (D2R) dopaminergic receptors, as well as tyrosine hydroxylase (TH) mRNA in dopaminergic areas of the adult, cocaine self-administered, rat brain that had been chronically exposed to CP or vehicle (VH) during periadolescence. Control groups with CP/VH exposure and no self-administration experience were also included. In adult females, CP administration induced an up-regulation of DAT in the caudate-putamen that was maintained after cocaine self-administration. In males, CP induced an increase in the D1Rs content in the nucleus accumbens shell, which was not evident after cocaine self-administration. CP also reduced the expression of D2Rs in CA1 irrespective of sex. Finally, an increase in D1Rs was observed in the substantia nigra following cocaine self-administration. These findings suggest that a dopaminergic component modulated by cannabinoids may underlie the enhanced cocaine self-administration previously observed in adult female rats.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 12/2010; 20(12):895-906. · 3.68 Impact Factor
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    ABSTRACT: Purpose To analyze brain metabolic response to acute cocaine in male and female Wistar rats with or without a history of cannabinoid exposure during periadolescence. Procedures The synthetic cannabinoid agonist CP 55,940 (CP) or its vehicle (VH), were administered to male and female rats during periadolescence. When these animals reached adulthood, saline and cocaine-induced changes in 2-deoxy-2-[18F]fluoro-D-glucose (FDG) uptake were studied by positron emission tomography. Results The baseline (post-saline) metabolism in the septal nuclei was higher in CP-females than in VH-females, although septal metabolism was lower in CP-females after cocaine, reaching similar values to those of VH-females at baseline. Cocaine did not affect metabolism in VH-females. Periadolescent cannabinoid treatment did not influence baseline metabolism in males although cocaine reduced the FDG uptake in the dorsal striatum of males that received the VH but not CP. Conclusions These results suggest that cannabinoids during periadolescence modify baseline and cocaine-evoked brain metabolism in a sex-dependent manner. In the case of CP-females, the involvement of septal metabolic alterations in their susceptibility to the rewarding effects of cocaine should be further investigated.
    Molecular imaging and biology: MIB: the official publication of the Academy of Molecular Imaging 09/2010; · 2.47 Impact Factor
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    ABSTRACT: PurposeTo analyze brain metabolic response to acute cocaine in male and female Wistar rats with or without a history of cannabinoid exposure during periadolescence. ProceduresThe synthetic cannabinoid agonist CP 55,940 (CP) or its vehicle (VH), were administered to male and female rats during periadolescence. When these animals reached adulthood, saline and cocaine-induced changes in 2-deoxy-2-[18F]fluoro-D-glucose (FDG) uptake were studied by positron emission tomography. ResultsThe baseline (post-saline) metabolism in the septal nuclei was higher in CP-females than in VH-females, although septal metabolism was lower in CP-females after cocaine, reaching similar values to those of VH-females at baseline. Cocaine did not affect metabolism in VH-females. Periadolescent cannabinoid treatment did not influence baseline metabolism in males although cocaine reduced the FDG uptake in the dorsal striatum of males that received the VH but not CP. ConclusionsThese results suggest that cannabinoids during periadolescence modify baseline and cocaine-evoked brain metabolism in a sex-dependent manner. In the case of CP-females, the involvement of septal metabolic alterations in their susceptibility to the rewarding effects of cocaine should be further investigated. Key wordsCannabinoids–Cocaine–Dorsal striatum–PET–Septal nuclei
    Molecular Imaging & Biology 01/2010; 13(3):411-415. · 3.10 Impact Factor
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    ABSTRACT: Pubertal and adolescent exposure to cannabinoids is associated with enduring alterations in anxiety and memory. However, periadolescence virtually remains unexplored. Here, we measured anxiety in the Elevated Plus Maze (EPM) in adult Wistar rats treated at periadolescence (P28-P38) with the cannabinoid agonist CP 55,940 (CP) (0.4 mg/kg; 2 ml/kg i.p., 1 daily injection), and we also defined their recognition memory in the novel object paradigm and spatial learning and memory in the water maze. Additionally, we measured the expression of hippocampal PSA-NCAM (Polysialic Acid-Neural Cell Adhesion Molecule) and long-term potentiation (LTP) as well as, given their role in mnemonic processing, the levels of plasma corticosterone and estradiol. We found that CP had no robust effects on anxiety or in recognition memory. In the water maze, only a slight decreased percentage of failed trials in the reference memory task and an improvement in an indirect index of attention were observed. However, we detected an up-regulation of hippocampal PSA-NCAM expression, only in CP-males, although this effect was not related to changes in LTP. No hormonal alterations were evident. Based on our data, minimal long-term effects on anxiety, learning and memory appear to result from cannabinoid exposure during the periadolescent period.
    Pharmacology Biochemistry and Behavior 11/2009; 93(4):482-90. · 2.61 Impact Factor
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    ABSTRACT: The Lewis (LEW) and Fischer 344 (F344) rat strains have been used as a model to study genetic vulnerability to drug addiction and they differ in their dopaminergic systems. We have studied the variation in the D1-like and D2-like receptors in distinct brain regions of LEW and F344 rats that self-administered morphine (1 mg/kg) for 15 days and also after different extinction periods (3, 7 and 15 days). Under basal conditions, binding to D1-like receptors in the olfactory tubercle and substantia nigra, and to D2-like receptors in the Pyriform cortex and hippocampal-CA1 was lower in LEW rats than in F344 rats. Conversely, the LEW rats exhibited stronger D2-like binding in the caudate-putamen. In most brain regions there was a decrease in D1-like binding in LEW rats after self-administration while the F344 animals displayed an increment. Additionally, D2 receptors of LEW rats were down-regulated after self-administration in the caudate-putamen and in the nucleus accumbens (shell and core divisions). Binding to D1-like receptors increased in both strains in the early phases of extinction, while in the later stages a differential regulation was observed between both strains. During the early phases of extinction only F344 rats showed alterations in D2-like receptor binding, however in the latter phases a specific modulation occurred in both strains. These differences in basal D1-like and D2-like receptor binding, and their differential modulation after self-administration and during extinction, may be reflected in the greater vulnerability to opiate addiction shown by LEW strain.
    Neuropharmacology 05/2009; 57(1):8-17. · 4.11 Impact Factor
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    ABSTRACT: Although dopamine and glutamate transmission has been implicated in cocaine dependence, the effects of the extinction of cocaine self-administration on protein transporters in both of these neurotransmitter systems remain unknown. We have used a yoked-box procedure to simultaneously test rats in triads, one rat that actively self-administered cocaine (CONT), while the other two received yoked injections of either cocaine (NON-CONT) or saline (SALINE). The brains in each triad were removed and processed for quantitative autoradiography immediately after the last session of cocaine self-administration (Day 0), or after 1, 5, or 10 days of extinction, and excitatory amino acid transporters (EAATs) and dopamine transporter (DAT) binding was examined. When compared to NON-CONT and SALINE animals, binding of radioligand to EAATs was significantly lower in the hippocampal CA1 field and the cerebellar cortex of CONT rats on Day 0, although it was significantly higher after 1 day of extinction in the infralimbic cortex. No differences in EAAT binding were observed after 5 or 10 days of extinction in any of the brain regions analyzed. In contrast and at all the time points of extinction, binding to DAT was significantly enhanced in CONT animals when compared to SALINE and NON-CONT rats in different forebrain and mesencephalic regions, including the nucleus accumbens, ventral tegmental area or caudate putamen. These results suggest that changes in protein transporter binding after cocaine self-administration and extinction are transient for EAAT while they are more enduring for DAT, and that they depend on the type of access to cocaine.
    Neuropharmacology 10/2008; 55(5):771-9. · 4.11 Impact Factor
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    ABSTRACT: Repeated administration of drugs of abuse is thought to induce a variety of persistent changes in both behavior and brain morphology, including modifications of neurons from the brain regions involved in addiction. We have studied the morphology of the basal dendritic arbor of cortical pyramidal neurons in addiction-resistant Fischer 344 strain rats that self-administered morphine. Pyramidal neurons in the prelimbic and motor cortex were intracellularly injected with Lucifer Yellow in fixed tissue and they were reconstructed in three dimensions using Neurolucida software. Morphine self-administration did not produce significant changes in the structure of the dendritic arbors or in the spine density of pyramidal neurons in either the prelimbic or motor cortex of F344 rats. Moreover, pyramidal cell morphology did not differ in these two cortical areas in saline self-administered animals. However, when the structure of these cortical pyramidal cells from Fischer 344 rats was compared with that previously reported in addiction-prone Lewis rats in the same cortical areas, significant morphological differences were found between both strains. Indeed, these differences were not only observed following morphine self-administration but also in saline self-administered control animals. We suggest that strain differences in the structure of pyramidal cells in certain cortical areas might represent an anatomical substrate for the distinct vulnerability to the reinforcing effects of morphine exhibited by Fischer 344 and Lewis rats in operant self-administration paradigms.
    Brain Research 09/2008; 1230:61-72. · 2.88 Impact Factor
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    ABSTRACT: Early cannabinoid consumption may predispose individuals to the misuse of addictive drugs later in life. However, there is a lack of experimental evidence as to whether cannabinoid exposure during adolescence might differently affect opiate reinforcing efficacy and the opioid system in adults of both sexes. Our aim was to examine whether periadolescent chronic exposure to the cannabinoid agonist CP-55,940 could exert sex-dependent effects on morphine reinforcing and the opioid system in adulthood. Morphine reinforcing was studied under a progressive ratio (PR) reinforcement schedule in adult male and female rats that previously acquired morphine self-administration under a fixed ratio 1 (FR1) schedule. Binding levels and functionality of mu-opioid receptors were also evaluated. Periadolescent cannabinoid exposure altered morphine self-administration and the opioid system in adult rats in a sex-dependent manner. CP-55,940-exposed males exhibited higher self-administration rates under a FR1, but not under a PR schedule. In females, CP-55,940 did not modify morphine self-administration under either schedule. Moreover, CP-55,940 also increased mu-opioid receptor levels in the subcallosal streak of pre-treated animals and decreased mu-opioid receptor functionality in the nucleus accumbens shell but again, only in males. Our data indicate that adult male rats exposed to the cannabinoid in adolescence self-administer more morphine than females, but only when the demands required by the schedule of reinforcement are low, which might be related to the decrease in mu-opioid receptor functionality in the NAcc-shell observed in these animals.
    Neuropharmacology 05/2008; 54(5):863-73. · 4.11 Impact Factor

Publication Stats

227 Citations
106.73 Total Impact Points

Institutions

  • 2012
    • Hospital Regional Universitario Carlos Haya Málaga
      Málaga, Andalusia, Spain
  • 2006–2012
    • National Distance Education University
      • Department of Psychobiology
      Madrid, Madrid, Spain
  • 2010
    • Complutense University of Madrid
      • Departamento de Medicina
      Madrid, Madrid, Spain