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At least 235 records · Page 13Linked to original sources

PubMed2005

Dehydroepiandrosterone (DHEA) attenuates cocaine-seeking behavior in the self-administration model in rats.

The aim of this study was to determine the possible involvement of the neurosteroid dehydroepiandrosterone (DHEA) in cocaine-seeking behavior in a self-administration model in rats. DHEA pretreatment (continued thereafter concomitantly with cocaine self-administration) attenuated cocaine-seeking behavior and elevated the levels of dopamine and serotonin in several brain regions relevant to cocaine addiction. Chronic cocaine self-administration induced elevation in brain DHEA, its sulfate ester, DHEAS, and pregnenolone. The increased brain DHEA following cocaine self-administration may serve as a compensatory protective mechanism geared to attenuate the craving for cocaine. Such anti-craving activity is further enhanced by DHEA treatment before and during cocaine self-administration.

Affect↗

PubMed1997

Kappa-opioid receptor agonist U50,488H modulates cocaine and morphine self-administration in drug-naive rats and mice.

Modulation of the reinforcing effects of cocaine and morphine by the kappa-opioid receptor agonist U50,488H (trans-3,4-dichloro-N-methyl-N-(2-1-pyrrolidinyl)-cyclohexyl-benzeace tamide) was studied by using the method of intravenous (i.v.) self-administration in drug-naive Wistar rats and DBA/2 mice. Self-administration of cocaine (by rats) and morphine (by mice) was readily initiated and showed an inverted U-shaped unit dose-response curve. Treatment with the kappa-opioid receptor agonist U50,488H dose dependently decreased the intake of both cocaine and morphine when offered in doses that readily initiated and sustained self-administration behavior. Interestingly, treatment with U50,488H induced self-administration behavior with lower sub-threshold doses of cocaine and morphine. With regard to the inverted U-shaped relation between the dose of the drug and the number of self-infusions, it seems that activation of the kappa-opioid receptor with U50,488H produced an almost parallel shift to the left, indicating an increased sensitivity of the animals for the reinforcing effects of cocaine and morphine. These data demonstrate an involvement of kappa-opioid systems in the neurobiological mechanisms underlying drug addiction in general, and sensitivity for drug reward in particular. Furthermore, the dual effect of kappa-opioid receptor agonists on drug self-administration may prompt further research into the mechanisms underlying the role of endogenous opioids in drug self-administration.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1983

Schedule-induction of nicotine self-administration.

Nicotine, although assumed to be an important factor in maintaining the use of tobacco products, has produced equivocal results when tested in drug self-administration studies using standard procedures with laboratory animals. Several recent studies however, have demonstrated nicotine self-administration using a procedure of schedule-induction. Schedule-induced behaviors occur as an adjunct to behavior controlled by an intermittent schedule of reinforcement and are thus not under control of the scheduled contingencies. Using schedule-induction procedures; oral, intravenous and inhaled self-administration of nicotine has been shown in rats, both rats and rhesus monkeys, and humans respectively. Although the self-administration of some doses of nicotine occurred without a concurrent schedule of intermittent reinforcement, schedule-induction results in responding maintained by lower doses of the drug and much more rapid initiation of self-administration. The result of such studies suggest an interaction between environmental factors, such as an intermittent schedule of other reinforcers, and nicotine's pharmacological effects. This interaction may be important in understanding the etiology and maintenance of human tobacco use.

Administration, Oral↗

PubMed1996

Combined effects of buprenorphine and a nondrug alternative reinforcer on i.v. cocaine self-administration in rats maintained under FR schedules.

Although previous studies have shown that pharmacological agents, such as buprenorphine, and alternative nondrug reinforcers, such as money or sweetened solutions, reduce cocaine self-administration, few studies have examined the combined effects of these two approaches. The purpose of the present study was to evaluate the effects of the opioid partial against buprenorphine (0.1 mg/kg) and concurrent access to either water or a glucose plus saccharin solution (G+S, 3% and 0.125% wt/vol) in rats self-administering intravenous (IV) cocaine (0.4 mg/kg per infusion) under fixed-ratio schedules (FR2, 8 or 32). One group had concurrent access to water and another group had concurrent access to G+S. After 3 consecutive days of stable cocaine self-administration, a single buprenorphine injection (0.1 mg/kg IV) was administered 30 min before the start of the experimental session for 3 consecutive days. To summarize the results, (1) the presence of an alternative non-drug reinforcer significantly reduced cocaine self-administration, (2) buprenorphine selectively decreased cocaine, but not water or G+S, self-administration; (3) the decrease in cocaine infusions by buprenorphine was greatest on the first day of buprenorphine administration; and (4) expressed as a percentage of baseline conditions, the combination of buprenorphine and G+S produced a greater decrease in cocaine self-administration than either buprenorphine or G+S alone. These results indicate that combined treatment with buprenorphine and concurrent access to a sweetened solution is a more effective strategy for reducing cocaine self-administration than either strategy alone.

Animals↗

PubMed1997

Dextromethorphan reduces intravenous cocaine self-administration in the rat.

Dextromethorphan is a widely used antitussive agent with non-competitive antagonistic effects at the excitatory amino acid receptors of the NMDA type. Since excitatory amino acid neurotransmission has been implicated in cocaine dependence, the aim of the present study was to evaluate the effects of acute systemic administration of dextromethorphan in rats trained to self-administer cocaine intravenously. The experiments were designed to evaluate the effects of dextromethorphan on responding for cocaine and cocaine reward magnitude. The hypothesis was that dextromethorphan could attenuate specific aspects of cocaine-seeking behavior thus providing a preclinical rationale for its clinical use. The results reported reveal that acute pretreatment with dextromethorphan (10-50 mg/kg i.p.) significantly reduced cocaine self-administration in rats self-administering the drug intravenously in a simple continuous reinforcement schedule. In addition, acute pretreatment with an effective dose of dextromethorphan (25 mg/kg) decreased cocaine self-administration in rats tested at various doses of cocaine (0.12-0.5 mg/injection). Finally, dextromethorphan (25 mg/kg) also reduced the absolute reward magnitude of cocaine as measured by responding for cocaine in a progressive ratio schedule. These results encourage further experimental and clinical studies to evaluate the potential use of dextromethorphan during various phases of the natural history of cocaine dependence in humans.

Animals↗

PubMed2002

The effect of tryptophan depletion on alcohol self-administration in non-treatment-seeking alcoholic individuals.

BACKGROUND: Alcohol self-administration in the laboratory has been used to evaluate pharmacological treatments and neurobiological mechanisms that underlie alcohol use in alcohol-dependent individuals. This study evaluated whether attenuation of serotonin synthesis via depletion of its precursor tryptophan reduces the amount of alcohol consumed in a self-administration paradigm in non-treatment-seeking individuals with alcohol use disorders. METHODS: Individuals with alcohol dependence (n = 8) and alcohol abuse (n = 4) who were not seeking treatment were recruited by advertisement and participated in two test days, 1 week apart. Each test session was preceded by administration of a concentrated amino acid drink that resulted in a rapid and significant decline in plasma free tryptophan (active depletion) or a similar drink containing tryptophan (placebo depletion). Tests were conducted in a randomized, double-blind fashion. The test session began with a cue exposure session where subjects were exposed to their favorite alcoholic beverage and asked to rate their craving for alcohol. After this, subjects were administered a priming drink designed to raise blood alcohol levels to 0.02 g%. Subjects then had the opportunity to drink up to eight additional drinks, each designed to raise blood alcohol levels by 0.02 g%, or to receive $3 for each drink not consumed over a 2-hr period. RESULTS: There were no significant differences in alcohol consumed or subjective intoxication with active tryptophan depletion compared with placebo. Self-reported craving correlated with the amount of alcohol consumed in the session. CONCLUSIONS: These data question the dependence of alcohol self-administration on the ongoing synthesis of serotonin.

Adolescent↗

PubMed1991

GR38032F, a serotonin 5-HT3 antagonist, fails to alter cocaine self-administration in rats.

Recent data have supported a role for serotonin (5-HT) in the self-administration of cocaine by laboratory rats. More specifically, it has been suggested that 5-HT3 receptor antagonists may be useful in the treatment of drug abuse. To assess this possibility, we compared the effects of the 5-HT3 antagonist, GR38032F, with the dopamine D2 receptor blocker, haloperidol, on the intravenous self-administration of cocaine (0.5 mg/kg/infusion) in rats. The serotonin antagonist (0.01, 0.1 or 1.0 mg/kg, IP) failed to alter self-administration (0.5 mg/kg/infusion). In contrast, haloperidol (0.125 mg/kg, IP) increased responding for cocaine (0.5 mg/kg/infusion), and shifted the dose-response curve for cocaine self-administration to the right. These data fail to support a role for the serotonin 5-HT3 receptor system in the reinforcing properties of this psychostimulant. Rather, the 5-HT1 or 5-HT2 receptors may be the critical subtype.

Animals↗

PubMed1992

[Studies on reinforcing effects of methylephedrine, caffeine and their mixture with intravenous-self administration in rhesus monkeys].

The reinforcing effects of methylephedrine hydrochloride (ME), anhydrous caffeine (CA) and their mixture (ME+CA) were studied by the intravenous cross self-administration experiment and by the progressive ratio experiment in four male rhesus monkeys each. In the intravenous cross self-administration experiment, ME, CA and ME+CA were found to have reinforcing effects. Self-administration rates above the level of cocaine, a typical reinforcing drug, were not observed in ME or CA alone, but observed in their mixture (120 + 126 micrograms/kg/inj.: M dose or 480 + 504 micrograms/kg/inj.: H dose). The minimum reinforcing doses were 120 micrograms/kg/inj. (M dose) for ME, 126 micrograms/kg/inj.: (M dose) for CA, and ME 30 micrograms+CA 32 micrograms/kg/inj. (L dose) for the mixture. Vomiting was observed during the session in monkeys which showed higher self-administration rates of ME and the mixture, and decreases in the rates were observed in these animals on the next day. One animal at H dose of the mixture, which showed a high self-administration rate on both the 1st and 2nd days, died after the end of the session on the 2nd day. In the progressive ratio experiment, the final ratios at 120 micrograms/kg/inj. of ME, 126 micrograms/kg/inj. of CA and the mixture of ME 120 micrograms/CA 126 micrograms/kg/inj. were almost equal to or less than that of saline (negative control). Thus, these drugs didn't show reinforcing effects at the above levels. However, a reinforcing effect was observed in three out of four monkeys administered 1920 micrograms/kg/inj. of ME, 2016 micrograms/kg/inj. of CA, and the mixture of ME 1920 and CA 2016 micrograms/kg/inj.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

A comparison of nucleus accumbens neuronal firing patterns during cocaine self-administration and water reinforcement in rats.

The firing patterns of nucleus accumbens (NA) neurons in the rat were recorded during cocaine self-administration and responding for water. Recordings were obtained from permanently implanted multiple-electrode arrays (eight microwires) inserted bilaterally into rostral portions of the NA in subjects (n = 18) exhibiting stable cocaine self-administration (0.33 mg/infusion), and during stable responding for water reinforcement. Electronically isolated and identified NA neurons exhibited four distinct patterns of phasic activity relative to the reinforced response. Three of these firing patterns were observed during both cocaine self-administration and water reinforcement sessions. Response-related activity was categorized by cells that showed an anticipatory increase in firing rate during the preresponse phase (type PR), and by cells that were excited (type RFE) or inhibited (type RFI) following the response in the reinforcement phase. PR and RFE cells showed significantly reduced peak firing during cocaine self-administration, compared to similar cells in water reinforcement sessions. A fourth type of NA firing pattern (type PR+RF) was observed only in cells recorded during cocaine self-administration sessions (Carelli et al., 1993b). PR+RF neurons exhibited two distinct peaks, one preceding the response and terminating at response completion (like PR cells), and a second peak immediately following the response (like RFE cells) with an inhibitory period between the two peaks (like RFI cells). The findings are discussed in terms of the role of the NA in mediating the reinforcing properties of both cocaine and water.

Animals↗

PubMed2004

Opposite effects of amphetamine self-administration experience on dendritic spines in the medial and orbital prefrontal cortex.

We studied the long-term effects of amphetamine self-administration experience (or sucrose reward training) on dendritic morphology (spine density) in nucleus accumbens (Nacc), medial (MPC) and orbital prefrontal cortex (OFC), and hippocampus (CA1 and dentate). Independent groups of rats were trained under a continuous schedule of reinforcement to nose-poke for infusions of amphetamine (0.125 mg/kg/inf) or to receive sucrose pellets during 2 h daily test sessions for 14-20 days. One month after the last training session, the brains were collected and processed for Golgi-Cox staining. We found that: (i) amphetamine self-administration experience selectively increased spine density on medium spiny neurons in the Nacc and on pyramidal neurons in the MPC; (ii) in contrast, amphetamine self-administration decreased spine density in the OFC, whereas sucrose-reward training increased spine density; and (iii) both amphetamine self-administration and sucrose-reward experience increased spines in the CA1, but had no effect in the dentate gyrus. Thus, amphetamine self-administration experience produces long-lasting and regionally-selective morphological alterations in rat forebrain--alterations that may underlie some of the persistent psychomotor, cognitive and motivational consequences of chronic drug exposure.

Adaptation, Physiological↗

PubMed2002

Metabolic mapping of the effects of cocaine during the initial phases of self-administration in the nonhuman primate.

Because most human studies of the neurobiological substrates of the effects of cocaine have been performed with drug-dependent subjects, little information is available about the effects of cocaine in the initial phases of drug use before neuroadaptations to chronic exposure have developed. The purpose of the present study, therefore, was to define the substrates that mediate the initial effects of cocaine in a nonhuman primate model of cocaine self-administration using the 2-[14C]deoxyglucose method. Rhesus monkeys were trained to self-administer 0.03 mg/kg per injection (N = 4) or 0.3 mg/kg per injection (N = 4) cocaine and compared with monkeys trained to respond under an identical schedule of food reinforcement (N = 4). Monkeys received 30 reinforcers per session, and metabolic mapping was conducted at the end of the fifth self-administration session. Cocaine self-administration reduced glucose utilization in the mesolimbic system, including the ventral tegmental area, ventral striatum, and medial prefrontal cortex. In addition, metabolic activity was increased in the dorsolateral and dorsomedial prefrontal cortex, as well as in the mediodorsal nucleus of the thalamus. These latter effects are distinctly different from those seen after the noncontingent administration of cocaine, suggesting that self-administration engages circuits beyond those engaged merely by the pharmacological actions of cocaine. The involvement of cortical areas subserving working memory suggests that strong associations between cocaine and the internal and external environment are formed from the very outset of cocaine self-administration. The assessment of the effects of cocaine at a time not readily evaluated in humans provides a baseline from which the effects of chronic cocaine exposure can be investigated.

Animals↗

PubMed2000

The pedunculopontine tegmental nucleus and the role of cholinergic neurons in nicotine self-administration in the rat: a correlative neuroanatomical and behavioral study.

The objective of this study was to determine whether the pedunculopontine tegmental nucleus plays a role in the maintenance of nicotine self-administration, and whether the ascending cholinergic projection from this nucleus to midbrain dopamine neurons in the ventral tegmental area might be involved. Studies were done with rats trained to self-administer nicotine intravenously. Self-administration was examined before and after the pedunculopontine tegmental nucleus was lesioned with the ethylcholine mustard aziridinium ion, a selective cholinergic toxin. Lesions were assessed qualitatively and quantitatively in histological sections stained for either nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry to identify cholinergic neurons, or for Nissl. Self-administration was also tested after an acute manipulation in which microinfusions of the nicotinic cholinergic antagonist dihydro-beta-erythroidine were made into the pedunculopontine tegmentum. Infusions of neurotoxin into the pedunculopontine tegmentum reduced nicotine self-administration behaviour when tested weeks later. Toxin treatment reduced the number of cholinergic neurons in the tegmentum, while largely sparing the non-cholinergic population in this area. Lesions were limited to the pedunculopontine area and did not extend to the neighboring laterodorsal tegmental nucleus or to the substantia nigra. Acute manipulation of the pedunculopontine tegmental nucleus with microinfusions of dihydro-beta-erythroidine also produced an attenuation of nicotine self-administration. Collectively these data show that the pedunculopontine tegmental nucleus is part of the neuronal circuitry mediating nicotine self-administration, and that the population of cholinergic neurons is likely a critical element.

Acetylcholine↗

PubMed1999

Depletion of brain serotonin following intra-raphe injections of 5,7-dihydroxytryptamine does not alter d-amphetamine self-administration across different schedule and access conditions.

OBJECTIVES: These experiments investigated the effects of selective serotonin (5-HT) depletion on intravenous self-administration of d-amphetamine. METHODS: Depletion of brain 5-HT levels was induced by injecting the serotonergic neurotoxin 5,7-dihydroxytryptamine (5, 7-DHT) into the dorsal and median raphe nuclei. Rats were then trained to self-administer d-amphetamine according to various schedule and access conditions via chronically indwelling intravenous catheters. RESULTS: Large reductions of brain 5-HT did not alter responding for a training dose of 120 microgram/kg d-amphetamine delivered according to a fixed ratio 1 schedule during 3-h sessions. When the dose of d-amphetamine was altered (0, 3.75, 7. 5, 15, 30, 60 microgram/kg per infusion) a characteristic inverted U-shaped dose response function was obtained. The 5-HT depleted rats showed increased responding for the lower doses of d-amphetamine, with a large significant increase in responding for the 7.5 microgram/kg dose. In these same rats, the suppressive effect of 10 mg/kg fluoxetine on d-amphetamine (60 microgram/kg) self-administration was prevented. The 5,7-DHT lesion also did not alter responding for d-amphetamine (120 microgram/kg) in longer (8 h) daily access sessions. Responding for d-amphetamine delivered on a progressive ratio schedule, in which response requirements increased for each successive infusion of d-amphetamine, was also determined in 5-HT depleted rats. The number of d-amphetamine infusions was not different from the number of infusions earned by sham-lesioned rats across a range of doses of d-amphetamine (7.5-60 microgram/kg). In a final experiment, spontaneous acquisition of self-administration of low doses of d-amphetamine (10 and 30 microgram/kg) was measured in 5-HT depleted and control rats. Again, self-administration behaviour in the 5-HT depleted rats did not differ from controls. CONCLUSIONS: These results provide no evidence that reducing 5-HT function alters the primary reinforcing effects of self-administered amphetamine. The increase in self-administration of a low dose of amphetamine observed in experiment 1 probably involves some other process such as increased resistance to extinction.

5,7-Dihydroxytryptamine↗

PubMed2006

Maternal separation and handling affects cocaine self-administration in both the treated pups as adults and the dams.

Repeated maternal separation of pups from dams is often used as an early life stressor that causes profound neurochemical and behavioral changes in the pups that persist into adulthood. The effects of maternal separation on both the dams and the treated pups as adults on cocaine self-administration were examined using four separation conditions: 15- or 180-min separation (MS15 and MS180), brief handling without separation (MS0), and a nonhandled group (NH). The separations and handling occurred daily on postnatal days 2 to 15. The acquisition of cocaine self-administration (0.0625-1.0 mg/kg/infusion) was evaluated in the treated pups as adults. The MS180 group acquired cocaine self-administration at the lowest dose tested (0.0625 mg/kg/infusion), whereas the MS15s did not respond for cocaine at rates greater than that seen with saline administration. The NH group received the greatest number of infusions and intake at the highest doses. After self-administration, no differences were observed between groups in activity of two liver carboxylesterases involved in the inactivation of cocaine, ES10 and ES4. Maternal separation affected cocaine self-administration in the dams as well. Although there was an overall significant affect of treatment on cocaine self-administration, the length of separation (15 or 180 min) did not affect cocaine self-administration on the dams. The MS0 dams averaged a greater number of infusions per session than NH group during the 1st week of acquisition. These data suggest that in addition to the profound changes that occur in pups as result of maternal separation, the dams are also susceptible to alterations in behaviors.

Aging↗

PubMed1999

Effects of D1 dopamine receptor agonists on oral ethanol self-administration in rats: comparison with their efficacy to produce grooming and hyperactivity.

In order to study the potential efficacy of dopamine receptor agonists in the treatment of alcohol abuse, the present study investigated the effects of several dopamine D1 receptor agonists with different intrinsic activities on ethanol self-administration in rats. In a separate experiment, the effects of two of the same compounds on saccharin self-administration were also studied. To investigate further the relationship between activity in reducing ethanol self-administration and efficacies to stimulate D1 receptors, the potencies of the agonists to reduce ethanol self-administration were compared with their potencies to produce hyperactivity and grooming, behaviors which are believed to involve stimulation of D1 receptors. Rats were trained to self-administer ethanol (10% v/v) orally in a free-choice two-lever operant task using a saccharin-fading procedure. Another group of rats was trained to self-administer a solution of saccharin (0.01% w/v) in a similar operant task. Pretreatment with full (R-6Br-APB, SKF 82958 and SKF 81297) and partial (SKF 38393 and SKF 77434) dopamine D1 receptor agonists dose-dependently decreased responding for ethanol. SKF 82958 and SKF 38393 also decreased responding for saccharin. Comparison of potencies to decrease ethanol self-administration with potencies to produce locomotor activity and grooming revealed that reduction of ethanol self-administration by D1 full agonists occurs at doses similar to those which produce grooming and locomotor activity. However, the partial agonists (and in particular, SKF 38393) reduced responding for ethanol at doses lower than those producing hyperactivity. The present results underline the involvement of D1 dopamine receptors in reward processes.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1998

Dietary additives and the acquisition of cocaine self-administration in rats.

The effects of dietary caffeine and the amount and palatability of food on the acquisition of cocaine (0.2 mg/kg) self-administration were examined. Using an autoshaping procedure, seven groups of 13 rats each were trained to press a lever resulting in a cocaine (0.2 mg/kg infusion under a fixed-ratio 1 (FR 1) schedule. One group had ad libitum access to caffeine- (0.2% w/w) admixed food. Three groups had access to 10 g, 20 g or ad lib food each day. Another three groups had the same three amounts of ground food with powdered saccharin (0.2% w/w) added. During daily 6-h autoshaping sessions, ten infusions were delivered each hour under a random-time 90-s schedule after a brief (15 s) extension of a retractable lever. These were followed by 6-h self-administration sessions, when the lever remained extended and cocaine infusions were available under an FR 1 schedule. The acquisition criterion was self-administration of a mean of 100 infusions over 5 days. Cocaine self-administration was accelerated in the caffeine group compared to the regular chow group. However, by 30 days nearly the same percentage of rats in the caffeine and regular food groups met the acquisition criterion. In the other six groups, as the amount of food increased, the rate of acquisition and percentage of rats per group meeting the acquisition criterion decreased. In the ad lib group, acquisition was further reduced when saccharin was added to food. In summary, dietary caffeine accelerated acquisition and a greater amount and increased palatability of food independently interfered with acquisition of cocaine self-administration in rats.

Animals↗

PubMed1996

Do programmes of medicine self-administration enhance patient knowledge, compliance and satisfaction?

Self-administration of medicine (SAM) programmes for hospital in-patients have become increasingly popular. Such programmes are considered to facilitate education and learning. A quasi-experimental, longitudinal study was carried out to examine and compare knowledge acquisition, drug compliance, and satisfaction between patients who self-administered their medications and those who did not. Improvements in knowledge and compliance with medication regimes could not be linked directly with a SAM programme. All patients had a high level of knowledge of their medications and appeared to be compliant with prescribed drug regimes. Study findings support the hypothesis that knowledge improves with time, regardless of how medications are administered, but do not support the hypothesis that patients who self-administrate are more knowledgeable about their medications than those who do not. Therefore, SAM programmes may improve patient knowledge but opportunities to obtain knowledge may not be unique to such programmes. The ward or unit philosophy may be such that other patients, who are less willing or able to participate directly in their own care, also have the opportunity to improve their knowledge.

Health Knowledge, Attitudes, Practice↗

PubMed2005

Effect of the cannabinoid CB1 receptor antagonist SR-141716A on ethanol self-administration and ethanol-seeking behaviour in rats.

RATIONALE: It has been suggested that endocannabinoid mechanisms are involved in the control of ethanol consumption. OBJECTIVES: The aims of the present study were (1) to evaluate the role of the endocannabinoid system in the control of operant ethanol self-administration and in the reinstatement of ethanol seeking, when induced by stress or conditioned stimuli and (2) to offer new insights on the specificity of such a role. METHODS: Rats were administered intraperitoneally with the selective cannabinoid CB1 receptor antagonist, SR-141716A, 30 min before operant self-administration or reinstatement sessions. Two schedules of reinforcement, the fixed-ratio 1 (FR1) and the progressive ratio (PR), were used to study 10% (w/v) alcohol and 5.0% sucrose self-administration. NaCl (2% w/v) intake in sodium-depleted rats was studied only under the FR1 program. RESULTS: Treatment with SR-141716A (0.3-3.0 mg/kg) significantly attenuated FR1 alcohol self-administration and lowered the break point for ethanol under PR. SR-141716A also markedly inhibited the reinstatement of alcohol seeking elicited by presentation of cues predictive of drug availability. Conversely, the cannabinoid antagonist did not prevent the reinstatement of alcohol seeking induced by foot-shock stress. Lever pressing for sucrose under FR1 and PR schedules was also significantly decreased by SR-141716A treatment, whereas the drug modestly and only at the highest dose decreased 2% NaCl self-administration. CONCLUSIONS: Results emphasize that endocannabinoid mechanisms play a major role in the control of ethanol self-administration and in the reinstatement of conditioned ethanol seeking. However, these effects extend to the control of operant behaviours motivated by natural rewards (i.e. sucrose). On the other hand, SR-141716A only weakly reduces NaCl self-administration in sodium-depleted rats, in which salt intake is largely controlled by homeostatic mechanisms. Overall, these observations demonstrate that the inhibition of operant behaviour following blockade of CB1 receptors by SR-141716A is linked to a reduction of reward-related responding and is not related to drug-induced motor deficits.

Alcohol Drinking↗