Biomedical subjects

José M Oliva

Publications and source records attributed to José M Oliva.

9 recordsLinked to original sources

PubMed2006

Gene transcription alterations associated with decrease of ethanol intake induced by naltrexone in the brain of Wistar rats.

Preclinical and clinical studies suggest that the administration of the opioid antagonist naltrexone decreases the intake of ethanol. However, the neuroplastic adaptations in the brain associated to reduction of ethanol consumption remains to be elucidated. The aim of the study was to identify gene transcription alterations underlying the attenuation of voluntary ethanol intake by administration of naltrexone in rats. Increasing doses of naltrexone (0.7 mg/kg, 4 days and 1.4 mg/kg/day, 4 days) to rats with acquired high preferring ethanol consumption (>3.5 g of ethanol/kg/day) decreased voluntary ethanol intake (50%). Voluntary ethanol consumption altered mu-opioid receptor function in the cingulate cortex, caudate-putamen (CPu), nucleus accumbens core (Acb C) and shell (Acb S), the expression of tyrosine hydroxylase (TH) in the ventral tegmental area and substantia nigra, proenkephalin (PENK) in the piriform cortex, olfactory tubercle, CPu, Acb C and Acb S, ventromedial nucleus (VMN) and paraventricular nucleus (PVN) of the hypothalamus, corticotropin releasing factor (CRF) in PVN, cannabinoid CB(1) receptor (CB1-R) in the CPu, hippocampus and VMN, and serotonin transporter (5-HTT) in the dorsal and median raphe nuclei. The reduction of ethanol intake induced by naltrexone was associated with a blockade or significant reduction of the changes produced by ethanol in the expression of these genes in key regions related to drug dependence. These results point to a role for the mu-opioid receptor, TH, PENK, CRF, CB1-R, and 5-HTT genes in specific brain regions in the modulation of neuroadaptative mechanisms associated to the decrease of ethanol intake induced by naltrexone.

Alcohol Drinking↗

PubMed2005

Time course of opioid and cannabinoid gene transcription alterations induced by repeated administration with fluoxetine in the rat brain.

This study examined the time course effects (8, 16 and 31 days) of fluoxetine administration (1 mg/kg, p.o./day) on serotonin transporter (5-HTT), opioid, tyrosine hydroxylase (TH) and cannabinoid CB1 receptor gene expressions in selected regions of the rat brain. Treatment with fluoxetine progressively decreased (35-55%) 5-HTT gene expression in dorsal raphe nucleus at 8, 16 and 31 days. The results revealed that fluoxetine administration decreased (30%) proenkephalin gene expression in nucleus accumbens shell (AcbS) and caudate-putamen (CPu) (31 days) but was without effect in nucleus accumbens core AcbC. A pronounced and time related decrease (25-65%) in prodynorphin gene expression was detected in AcbC, AcbS, CPu, hypothalamic supraoptic and paraventricular nuclei at all time points as well as in proopiomelanocortin gene expression (20-30%) in the arcuate nucleus (ARC) of the hypothalamus. On days 16 and 31, tyrosine hydroxylase gene expression in ventral tegmental area and substantia nigra and cannabinoid CB1 receptor gene expression in the CPu decreased (approximately 45-50% from vehicle). In conclusion, fluoxetine by inhibiting the reuptake of serotonin produced pronounced and time related alterations in genes involved in the regulation of emotional behaviour, suggesting that these neuroplastic changes may be involved, at least in part, in the clinical efficacy of this drug in neuropsychiatric disorders.

Animals↗

PubMed2004

Interactions between cannabinoid and opioid receptor systems in the mediation of ethanol effects.

Over the past few years, advances in the investigation of the neurochemical circuits involved in the development and treatment of alcohol dependence have identified peptides and receptors as potential key targets in the treatment of problems related to alcohol consumption. The endogenous opioid system is modified by alcohol intake in areas of the brain related to reward systems, and differential basal levels of opioid gene expression are found in rodents with a high preference for ethanol. This suggests a greater vulnerability to alcohol consumption in relation to differences in genetic background. Further evidence of the involvement of opioid peptides in alcohol dependence is the ability of the opioid antagonist naltrexone to reduce alcohol intake in animal models of dependence and in alcohol-dependent patients. Abundant evidence indicates that the activation of cannabinoid receptors stimulates the release of opioid peptides, therefore the cannabinoid receptor antagonists may presumably alter opioid peptide release, thus facilitating the reduction of ethanol consumption. However, little is known about the effects of ethanol on the endogenous cannabinoid system, the vulnerability of cannabinoid receptors to alcohol intake or their neurochemical implications in reducing consumption of alcohol. In this paper, we review the role of opioid and cannabinoid receptor systems, their vulnerability to alcohol intake and the development of dependence, and the targeting of these systems in the treatment of alcoholism.

Alcohol Drinking↗

PubMed2004

Repeated administration with Delta9-tetrahydrocannabinol regulates mu-opioid receptor density in the rat brain.

Several studies have demonstrated reciprocal, as well as synergistic interactions between cannabinoid and opioid systems. The aim of this study was to explore the time-related effects of repeated administration of Delta9-tetrahydrocannabinol on mu-opioid receptor autoradiography in various brain regions of the rat. To this aim, the effects of Delta9-tetrahydrocannabinol (Delta9-THC, 5 mg/kg/day; i.p.) were examined after 1, 3, 7 and 14 days of repeated administration on regions containing mu-opioid receptors: (i) forebrain [caudate-putamen, nucleus accumbens (core and shell) and piriform cortex]; (ii) amygdala (medial pars and cortical posteromedial pars), hypothalamus (ventromedial and dorsomedial nuclei, zona incerta), hippocampal regions (CA1, CA2, CA3, dentate girus), hindbrain (substantia nigra and ventral tegmental area); and (iii) thalamus, including 12 thalamic nuclei. In most of these regions, repeated cannabinoid administration increases mu-opioid receptor density; however, the onset, degree of magnitude reached and time-related effects produced by administration with Delta9-tetrahydrocannabinol are dependent upon the brain region examined. It appears that the major increase in mu-opioid receptor density occurs 1 and 3 days after Delta9-THC administration. In some regions, this increase is maintained and, for most of the brain areas examined, this effect is no longer significant by 14 days of administration, suggesting tolerance to cannabinoid treatment. Taken together, the results of this study suggest that cannabinoids produce a time-related differential responsiveness in mu-opioid receptor density in several brain areas that may be relevant to an understanding of the alterations associated with cannabinoid exposure.

Animals↗

PubMed2004

Spontaneous cannabinoid withdrawal produces a differential time-related responsiveness in cannabinoid CB1 receptor gene expression in the mouse brain.

This study aimed to examine the behavioural and neurochemical (cannabinoid CB1 receptor gene expression) changes induced by spontaneous cannabinoid withdrawal in mice. Tolerance was assessed by measuring rectal temperature and motor activity in the open-field test after CP-55, 940 administration. Cannabinoid withdrawal symptoms were determined by measuring motor activity and behavioural signs of abstinence. Cessation of CP-55, 940 treatment in tolerant mice induced a spontaneous time-dependent behavioural withdrawal syndrome consisting of marked increases (140%) in motor activity, number of rearings (170%), decreases in grooming (57%), wet dog shakes (73%) and rubbing behaviours (74%) on day 1, progressively reaching values similar to vehicle-treated mice on day 3. Interestingly, this spontaneous cannabinoid withdrawal resulted in CB1 gene expression upregulation (20-30%) in caudate-putamen, ventromedial hypothalamic nucleus, central amygdaloid nucleus and CA1, whereas in the CA3 field of hippocampus, a significant decrease (15-20%) was detected. Taken together, the results of this study suggest that cessation of CP-55, 940 administration in tolerant mice produces a behavioural cannabinoid withdrawal syndrome and a selective and differential responsiveness in CB1 receptor gene expression in several brain regions of the mice. These findings further suggest a time and regional differential role for cannabinoid receptors in short- and long-term neuroadaptations that occur after exposure to cannabis derivatives.

Animals↗

PubMed2003

Behavioural and gene transcription alterations induced by spontaneous cannabinoid withdrawal in mice.

This study examined behavioural signs that occur during tolerance development to cannabinoid treatment and hormonal and gene expression alterations induced by spontaneous cannabinoid withdrawal in mice. Tolerance to CP-55,940 treatment developed for hypothermia, ambulatory and exploratory locomotor activity. Cessation of cannabinoid treatment resulted in a behavioural withdrawal syndrome characterized by a pronounced increase in ambulatory activity and rearings. Corticosterone plasma concentrations dramatically increased 24 and 72 h after cessation of cannabinoid treatment. Similarly, an increase (40%) in cannabinoid [35S]GTPgammaS binding autoradiography was detected on days 1 and 3 of abstinence. Spontaneous cannabinoid withdrawal produced time-related significant alterations in gene transcription: (i) decreased (20%) tyrosine hydroxylase (TH) mRNA levels in the ventral tegmental area and increased (50%) in substantia nigra; (ii) increased proenkephalin (PENK) gene expression more than 100% in caudate-putamen, nucleus accumbens, olfactory tubercle and piriform cortex; (iii) increased (20-40%) pro-opiomelanocortin (POMC) gene expression in the arcuate nucleus of the hypothalamus. These results suggest that spontaneous cannabinoid withdrawal occur after cessation of CP-55,940 treatment. This 'syndrome' includes behavioural, hormonal and gene transcription alterations that seems to be part of the regulation of neuronal plasticity induced by spontaneous cannabinoid withdrawal.

Animals↗

PubMed2002

Neuroadaptive changes in NMDAR1 gene expression after extinction of cocaine self-administration.

The aim of the present work was to study the time course effects in levels of mRNA encoding N-methyl-d-aspartate receptor subunit 1 (NMDAR1) after long-term cocaine self-administration (1 mg/kg/ injection) and its extinction using a yoked-box procedure. NMDAR1 content was measured by quantitative in situ hybridization histochemistry in prefrontal cortex, caudate-putamen, nucleus accumbens, olfactory tubercle, and piriform cortex immediately after cessation of the last session of cocaine self-administration (Day 0) and 1, 5, and 10 days after the extinction period. The results show that long-term cocaine self-administration and its extinction alter NMDAR1 gene expression in these forebrain regions, and that the changes depend upon the brain region examined and the type of cocaine administration (contingent, noncontingent, and saline). Compared to saline and noncontingent cocaine administration, contingent cocaine produced an up-regulation in NMDAR1 gene expression on Day 0 in all the brain regions analyzed. NMDAR1 levels of contingent animals decreased progressively in the absence of cocaine, and the decrement persisted 10 days after the extinction of cocaine self-administration behavior in all the forebrain areas, with the exception of olfactory tubercle. In contrast, noncontingent cocaine administration did not produce any change in NMDAR1 gene expression on Day 0, and extinction resulted in an increase of NMDAR1 mRNA content on Days 1 and 5 and returned to control (saline) values on Day 10. These results suggest that an interaction between environmental stimuli and the pharmacological action of cocaine during drug self-administration and its extinction may represent an important factor in the regulation of cocaine effects on NMDAR1 gene expression.

Analysis of Variance↗

PubMedDate not supplied

Chronic ethanol consumption regulates cannabinoid CB1 receptor gene expression in selected regions of rat brain.

AIMS: The aim of this study was to examine the effects of chronic ethanol consumption in cannabinoid CB(1) receptor gene expression in Wistar rats. METHODS: Rats were exposed to a bottle containing a solution of ethanol (10% v/v) and saccharin (0.25% w/v) for 52 days. At the end of this period, rats were killed by decapitation and cannabinoid CB(1) receptor gene expression was measured by in situ hybridization histochemistry. RESULTS: Our results indicated that chronic ethanol consumption reduced cannabinoid CB(1) receptor gene expression in caudate-putamen (CPu) (24%), ventromedial nucleus of the hypothalamus (VMN) (43%), CA1 (27%) and CA2 (22%) fields of hippocampus and increased dentate gyrus (DG) (30%). CONCLUSIONS: These results reveal for the first time that prolonged exposure to ethanol produces marked alterations in cannabinoid CB(1) receptor gene expression in selected regions of the rat brain, supporting an interaction between ethanol consumption and the endogenous cannabinoid receptor. Furthermore, these findings suggest that cannabinoid CB(1) receptor may be considered as a new pharmacological target for treating ethanol dependence.

Alcohol Drinking↗

PubMedDate not supplied

Differences in basal cannabinoid CB1 receptor function in selective brain areas and vulnerability to voluntary alcohol consumption in Fawn Hooded and Wistar rats.

AIM: To specify the functional activity of cannabinoid CB1 receptor in alcohol-preferring Fawn Hooded and alcohol nonpreferring Wistar rats under naïve conditions. METHOD: Cannabinoid CB1 (WIN-55,212)-stimulated [35S]-GTPgammas binding autoradiography, and cannabinoid CB1 receptor gene expression were measured in rats of both strains that received only water. RESULTS: Cannabinoid CB1 receptor stimulated [35S]-GTPgammas binding was significantly lower in cingulate cortex (Cg), caudate-putamen (CPu), nucleus accumbens (Acc), ventromedial hypothalamic nucleus (VMN), amygdaloid area (AMG), fields (CA1, CA3) of the hippocampus and dentate gyrus (DG) in Fawn Hooded than in Wistar rats, whereas no differences were found either in substantia nigra pars reticulata (SNr) nor CA2 field of the hippocampus. In addition, cannabinoid CB1 receptor gene expression was lower in Cg, CPu, VMN and CA3 field of the hippocampus in Fawn Hooded than in Wistar rats. CONCLUSIONS: We speculate that lower cannabinoid function appears to be related to greater vulnerability to alcohol consumption. Cannabinoid CB1 receptor may represent a key target in the treatment of alcohol dependence.

Alcohol Drinking↗