Search results for "COCAINE"
showing 10 items of 143 documents
Acquisition and reinstatement of MDMA-induced conditioned place preference in mice pre-treated with MDMA or cocaine during adolescence
2009
Those who take ecstasy are more likely to consume other drugs than non-users with cocaine abuse being reported by 75.5% of high school student MDMA (+/- 3,4-methylenedioxymetamphetamine hydrochloride) users. The aim of this work was to evaluate the effects of exposure during adolescence to MDMA, cocaine or to both drugs on the MDMA-induced conditioned place preference (CPP) in adult mice. Animals received two daily administrations of saline, 10 mg/kg of MDMA, 25 mg/kg of cocaine or 10 mg/kg of MDMA plus 25 mg/kg of cocaine over 3 days (from PD28 to 30). Three weeks after pre-treatment, the MDMA-induced CPP procedure was initiated (PD52). Acquisition of CPP was induced with a sub-threshold d…
Effect of memantine and CNQX in the acquisition, expression and reinstatement of cocaine-induced conditioned place preference
2006
The present study evaluates the effect of memantine, a non-competitive N-methyl-d-aspartate (NMDA) glutamate receptor antagonist and CNQX, an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptor antagonist on the rewarding effects of cocaine in mice, using the conditioned place preference (CPP) paradigm. Cocaine-induced CPP was studied pairing this drug with different memantine or CNQX doses during either the acquisition or the expression phase of the procedure. Once CPP was established, and the preference extinguished, reinstatement was induced by a priming dose of cocaine. Both antagonists, which in themselves do not present motivational actions on the preferen…
Increased toxicity of cocaine on human hepatocytes induced by ethanol: role of GSH.
1999
Increased toxicity of cocaine to human hepatocytes is observed when cells are simultaneously incubated with ethanol. Ethanol might exacerbate cocaine hepatocyte toxicity by three different pathways: a) by increasing the oxidative metabolism of cocaine and hence the oxidative damage; b) by the formation of a more toxic metabolite, namely cocaethylene; or c) by decreasing the defence mechanisms of the cell (i.e. GSH). In the present study, experiments were conducted to investigate the feasibility of these hypotheses. In hepatocytes preincubated for 48 hr with ethanol, neither significant changes in cocaine metabolism nor cytotoxicity were found despite differences in hepatocyte p-nitrophenol …
The high affinity dopamine uptake inhibitor, JHW 007, blocks cocaine-induced reward, locomotor stimulation and sensitization
2009
The discovery and evaluation of high affinity dopamine transport inhibitors with low abuse liability is an important step toward the development of efficacious medications for cocaine addiction. We examined in mice the behavioural effects of (N-(n-butyl)-3Ά-[bis(4Ά-fluorophenyl)methoxy]-tropane) (JHW 007), a benztropine (BZT) analogue that blocks dopamine uptake, and assessed its potential to influence the actions of cocaine in clinically-relevant models of cocaine addiction. In the conditioned place preference (CPP) paradigm, JHW 007 exposure did not produce place conditioning within an ample dose range but effectively blocked the CPP induced by cocaine administration. Similarly, in the CP…
Social defeat-induced increase in the conditioned rewarding effects of cocaine: Role of CX3CL1
2019
Abstract Social stress is associated with higher vulnerability to drug use, as it enhances the reinforcing effects of psychostimulants in rodents. Furthermore, continued or severe stress induces a proinflammatory state of microglial activation and augmented cytokine production. The aim of the present work was to evaluate the role of fractalkine [C-X3-C motif ligand 1 (CX3CL1)], an inflammatory chemokine, in the increased conditioned rewarding effects of cocaine in animals exposed to social defeat stress. In addition, we measured the signaling cascade pathway of CX3CL1 in the hippocampus (HPC) (including p-ERK/ERK, p-p38/p38 MAPK, p-p65/p65 NFκB and p-CREB/CREB ratios). The glutamate recepto…
Intermittent voluntary wheel running promotes resilience to the negative consequences of repeated social defeat in mice
2022
A novel approach to reduce the incidence of substance use disorders is to promote resilience to stress using environmental resources such as physical exercise. In the present study we test the hypothesis that Voluntary Wheel Running (VWR) during adolescence blocks the negative consequences of stress induced by intermittent repeated social defeat (IRSD). Four groups of adolescent male C57BL/6 mice were employed in the experiment; two groups were exposed to VWR (1 h, 3 days/week) from postnatal day (PND) 21 until the first social defeat (PND 47), while the remaining two groups did not have access to activity wheels (controls). On PND 47, 50, 53 and 56 mice, who had performed VWR, were exposed…
Discrimination between cocaine-associated context and cue in a modified conditioned place preference paradigm: role of the nNOS gene in cue condition…
2009
The conditioned place preference (CPP) paradigm entails appetitive learning and is utilized to investigate the motivational effects of drug and natural reward in rodents. However, a typical CPP design does not allow dissociation between cue- and context-dependent appetitive learning. In humans, context and cues that had been associated with drug reward can elicit conditioned response and drug craving. Therefore, we investigated (a) methods by which to discriminate between cue- and context-dependent appetitive learning, and (b) the role of the neuronal nitric oxide synthase (nNOS) gene in appetitive learning. Wild-type (WT) and nNOS knockout (KO) mice were trained by cocaine (20 mg/kg) in a …
Intermittent cortical stimulation evokes sensitization to cocaine and enduring changes in matrix and striosome neuron responsiveness
2005
Both the behavioral sensitization syndrome and the changes in the responsiveness of striatal neurons evoked by chronic cocaine exposure may be linked to enhanced neocortical activity, yet a direct demonstration of the effects of cortical stimulation on these parameters is lacking. We have found that repeated stimulation of the rat prelimbic cortex with picrotoxin (0.25 microg/0.25 microl, five injections on alternate days followed by 7-day withdrawal) contributed to increase c-Fos protein expression in the striosomes of the dorsolateral striatum, while producing the opposite effect in the matrix compartment, after a single exposure to cocaine (25 mg/kg). Moreover, rats exposed to cortical s…
Effect of adolescent exposure to MDMA and cocaine on acquisition and reinstatement of morphine-induce CPP
2007
It is well known that an elevated percentage of ecstasy users also consume cocaine. Recently, it has been reported that a high frequency of heroin smokers first consumed heroin under the effects of ecstasy with the hope of reducing the stimulant effects of the latter drug. The aim of the present study was to evaluate the effect of exposure to MDMA and cocaine during adolescence on morphine-induced conditioned place preference (CPP) and reinstatement in adulthood. In the first experiment, adolescent mice were exposed to six injections of MDMA and three weeks later their response to the reinforcing properties of 40 mg/kg of morphine was evaluated using the CPP paradigm. All the treatment grou…
The dopamine uptake inhibitor 3 alpha-[bis(4'-fluorophenyl)metoxy]-tropane reduces cocaine-induced early-gene expression, locomotor activity, and con…
2009
Benztropine (BZT) analogs, a family of high-affinity dopamine transporter ligands, are molecules that exhibit pharmacological and behavioral characteristics predictive of significant therapeutic potential in cocaine addiction. Here, we examined in mice the effects of 3 alpha-[bis(4'-fluorophenyl)metoxy]-tropane (AHN-1055) on motor activity, conditioned place preference (CPP) and c-Fos expression in the striatum. AHN-1055 produced mild attenuation of spontaneous locomotor activity at a low dose (1 mg/kg) and weak stimulation at a higher dose (10 mg/kg). In parallel, the BZT analog significantly increased c-Fos expression in the dorsolateral caudoputamen at the high dose, whereas producing ma…