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PubMed2002

Ethanol self-administration in Maudsley reactive and Maudsley nonreactive inbred rats.

This study was performed to investigate ethanol self-administration in inbred Maudsley rats, which were selected for differences in stress susceptibility and which often differ in their home cage ethanol consumption. Adult, male, Maudsley reactive (MR/Har) and Maudsley nonreactive (MNRA/Har) rats were tested in a standard protocol for the sucrose-substitution procedure for the initiation of self-administration of ethanol in an operant setting. Before and after initiation for self-administration in the operant setting, rats were tested for home cage consumption of 10% (vol./vol.) ethanol in a two-bottle test for 14 consecutive days. During the sucrose-substitution procedure, MNRA/Har rats consumed more sucrose and ethanol than did MR/Har rats. In addition, MNRA/Har rats self-administered a greater amount of ethanol during a concentration manipulation with the use of a fixed ratio (FR) 4 response requirement. However, both strains self-administered low amounts of 10% ethanol (MNRA/Har, 0.15 g/kg/day; MR/Har, 0.08 g/kg/day) after concentration manipulation compared with those observed in outbred rats and alcohol-preferring rats tested under identical conditions in other studies. Both MR/Har and MNRA/Har rats markedly increased their ethanol intake in the home cage after the initiation protocol, but there was no difference between MR/Har and MNRA/Har on that measure. The failure of MR/Har rats to self-administer ethanol was inconsistent with their home cage drinking in other studies, and this is distinctly different from the self-administration pattern of high-alcohol-drinking rat lines tested in this paradigm.

Alcohol Drinking↗

PubMed1996

Amphetamine self-administration by humans: modulation by contingencies associated with task performance.

The effect of task performance feedback and associated monetary earnings on drug self-administration were evaluated using eight subjects in a residential laboratory setting. The hypothesis was that if subjects believed that d-amphetamine impaired performance and reduced monetary earnings, d-amphetamine self-administration would decrease. Subjects performed computer tasks every day: on certain days that they received capsules, subjects were given bogus feedback regarding their performance ("better" or "worse" than average). On sample days, subjects were required to take d-amphetamine (10 mg BID) or placebo (0 mg BID) capsules. On choice days, subjects could choose between either d-amphetamine or placebo. Subjects received feedback on their task performance on 2 sample days and 2 of 4 choice days. Subjects received no feedback on the remaining two choice days. When subjects received no feedback, they chose d-amphetamine over placebo 78% of the time, and when they were given better feedback messages, they chose d-amphetamine 87.5% of the time. In contrast, d-amphetamine self-administration decreased significantly to 25% when subjects were told that it impaired their performance on work tasks and resulted in reduced earnings. In reality, d-amphetamine had little effect on work task performance. However, compared to placebo, d-amphetamine significantly increased subjective ratings of "Stimulated" and "Good Drug Effect" and significantly decreased ratings of "Tired" and "Sleepy." These results demonstrate that d-amphetamine served as a reinforcer under conditions in which drug self-administration did not influence monetary earnings, but that d-amphetamine self-administration could be modified by feedback/monetary earnings. Thus, contingencies associated with performance have important implications for drug use in the workplace.

Adult↗

PubMed1991

Caffeine self-administration, withdrawal, and adverse effects among coffee drinkers.

Twenty-two coffee drinkers (three to seven cups per day) underwent repeated double-blind trials to test for caffeine self-administration, withdrawal, and adverse effects. Each trial consisted first of a randomized crossover period of 1 day of decaffeinated coffee and 1 day of caffeinated coffee (100 mg) to assess withdrawal and adverse effects of caffeine. Next, subjects were given 2 days of concurrent access to the two coffees. The relative use of the two coffees was used to assess caffeine self-administration. Reliable caffeine self-administration occurred in three of 10 subjects in study 1 and seven of 12 subjects in study 2. Withdrawal symptoms were headaches, drowsiness, and fatigue. The major adverse effect from self-administration was tremulousness. The occurrence of headaches on substitution of decaffeinated coffee prospectively predicted subsequent self-administration of caffeine. These results indicate that some coffee drinkers exhibit signs of a caffeine dependence, ie, they self-administer coffee for the effects of caffeine, have withdrawal symptoms on cessation, and experience adverse effects.

Adult↗

PubMed1999

Tonic firing of rat nucleus accumbens neurons: changes during the first 2 weeks of daily cocaine self-administration sessions.

Activity of single neurons in the nucleus accumbens (NAcc) of rats was recorded extracellularly on the 2nd and 15th days of intravenous cocaine self-administration. Each of the two electrophysiological recording sessions consisted of three successive phases: a pre-drug baseline recording period, a cocaine self-administration session, and a post-drug recording period. Firing of individual neurons was typically inhibited during the self-administration session, relative to the pre-drug period. The inhibition was greater on the 15th day relative to the 2nd day. Additionally, firing rates during the pre-drug period and the self-administration session were typically lower on the 15th day as compared to the 2nd day. The present data are consistent with previous acute electrophysiological findings and are in line with the hypothesis that repeated drug self-administration engenders changes in the mesoaccumbens pathway that contribute to drug addiction.

Action Potentials↗

PubMed2003

Temporal upregulation of prodynorphin mRNA in the primate striatum after cocaine self-administration.

Several human and rat studies suggest that the striatal dynorphin system is important for neuroadaptation following cocaine exposure. In the current study, prodynorphin (PDYN) mRNA expression was examined in monkeys at initial and chronic phases of cocaine self-administration. Adult Rhesus monkeys were trained to self-administer food (banana flavoured pellets) or cocaine (0.03 or 0.3 mg/kg per injection) on a fixed interval 3-min schedule for 5 or 100 sessions. Each session ended after 30 reinforcers were delivered. The PDYN mRNA expression was analysed in the precommissural striatum using in situ hybridization histochemistry. We found a specific activation of PDYN mRNA expression in the limbic-innervated patch/striosome compartment of the dorsal caudate and dorsal putamen during the initial (i.e. 5 day) phase of the high dose cocaine self-administration. After 100 days of the high dose exposure, the patch/striosome compartment remained activated, but an increase in PDYN mRNA levels was also evident in the sensorimotor-connected matrix compartment of the caudate. Neither self-administration phase resulted in significant changes in the corresponding striatal regions of the low dose cocaine-exposed primates. Moreover, cocaine self-administration failed to alter the PDYN mRNA expression in high- or low-expressing PDYN cell populations in the nucleus accumbens during any condition studied. These results demonstrate the vulnerability of the dorsal striatum (in particular the caudate) to neuroadaptations following long-term high dose cocaine self-administration. In addition, the temporal nature of the changes in PDYN gene expression within the striatal compartments could reflect a change in drug responsivity that occurs during the transition to drug dependence.

Animals↗

PubMed2001

Location preference related to smoked heroin self-administration by rhesus monkeys.

RATIONALE: Although common in humans, little is known about the reinforcing efficacy of smoked heroin in laboratory animals. OBJECTIVES: To evaluate the reinforcing efficacy of smoked heroin in non-opioid dependent, non-human primates. METHODS: Self-administration and location-preference measures were obtained by having monkeys live in two chambers with heroin self-administration (0, 0.3, 0.6 mg/kg; eight dosings available per day) specific to one chamber and no commodity available in the other chamber. Operant responding reinforced by smoked heroin provided a self-administration measure of reinforcement, and the length of time monkeys spent in the heroin-associated chamber provided a location preference estimate of reinforcing efficacy. RESULTS: Four of six monkeys acquired heroin self-administration: these monkeys completed six to eight smoking trials each day when either of the active heroin doses was available. Urine toxicology confirmed that monkeys were absorbing the smoked heroin. The number of completed smoking trials rapidly decreased under extinction conditions, indicating that smoked heroin was an efficacious reinforcer using the self-administration measure. Monkeys developed a location preference for the chamber where heroin was self-administered, indicating that smoked heroin was an efficacious reinforcer using the location-preference measure. CONCLUSIONS: Smoked heroin is an efficacious reinforcer in non-opioid dependent rhesus monkeys as measured using a self-administration procedure and estimated using a location-preference procedure.

Animals↗

PubMed1996

Dopamine overflow in the nucleus accumbens during extinction and reinstatement of cocaine self-administration behavior.

Both cocaine and cocaine-associated stimuli can reinstate extinguished self-administration behavior in animals. It has been suggested that reinstatement of drug-seeking behavior may be mediated by enhanced dopamine (DA) neurotransmission. To examine this hypothesis, DA overflow was measured in the nucleus accumbens (NAc) of rats during both extinction and cocaine-induced reinstatement of self-administration behavior. Rats were either allowed to self-administer cocaine for 3 hours daily for 14 days, or they received yoked administration of saline. A stimulus light above the lever was illuminated during drug delivery. Baseline DA overflow was measured in the NAc, using in vivo microdialysis 7 to 8 days after the last self-administration session. The rats were then placed into the operant chambers and allowed to respond in extinction for 90 minutes, during which responses resulted in presentation of the stimulus light. The rats then received a cocaine injection that reinstated self-administration behavior. Contrary to our hypothesis, cocaine-experienced animals exhibited less DA overflow in the NAc relative to controls during both extinction and reinstatement.

Animals↗

PubMed1976

Mazindol self-administration in the rhesus monkey.

The ability of the intravenous administration of mazindol (SaH 42-548) to act as a reinforcer in monkeys previously conditioned to self-administer cocaine was ascertained. Unit dosages i.e. dosage per injection, of 50 and 100 mug/kg resulted in self-administration rates significantly greater than that which occurred with saline. An inverse relationship existed between unit dosage and frequency of self-administration over the unit dosage range 50-200 mug/kg. The total mazindol dosage self-administration per session was however independent of unit dosage. Approximately 2-3 mg/kg was self-administered by each animal during a 4 hr session at each of the 3 unit dosages. This tends to indicate that the 200 mug/kg unit dosage was also reinforcing even though the self-administration rate was similar to that of saline. This study indicates that mazindol can serve as a reinforcer and that the relationship between total session intake, unit dosage, and self-administration frequency of mazindol are similar to these seen with other reinforcing psychomotor stimulant drugs.

Animals↗

PubMed1988

A comparison of the effects of intra-accumbens injections of amphetamine and morphine on reinstatement of heroin intravenous self-administration behavior.

In rats previously trained to self-administer heroin intravenously, the application of morphine directly to the ventral tegmental area (VTA) has been shown to reinstate responding after a period of extinction, suggesting that the activation of mesolimbic dopamine neurons might underlie the priming effects of i.v. injections of opiates and stimulants found previously. In the present experiments rats were trained to self-administer heroin intravenously. Following extinction training, and after a period of at least 30 min of no responding, bilateral microinjections of either 0.5 microliter saline or 10 micrograms/0.5 microliter (+)-amphetamine sulfate were made into the N. accumbens. Amphetamine, but not saline reinstated self-administration behavior for about 1 h. In contrast, bilateral intra-accumbens injections of either 5 or 10 micrograms/0.5 microliter morphine sulfate to these same animals led to only infrequent responses late in the 90 min session. Both drugs increased locomotor activity measured in independent tests. Because the locomotor activity produced by intra-accumbens morphine occurs independent of the mesolimbic dopamine system, unlike that produced by VTA morphine and intra-accumbens amphetamine, and because it does not show sensitization, it is argued that the reinstatement effects of opiates and stimulants on self-administration behavior are mediated by the mesolimbic dopamine system, and may be related to the ability of opiates and stimulant drugs to cause sensitization within that system.

Amphetamine↗

PubMed2002

Effects of 7-OH-DPAT on cocaine-seeking behavior and on re-establishment of cocaine self-administration.

Effects of the D2-like dopamine agonist, 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT), on cocaine-seeking behavior and re-establishment of cocaine self-administration were examined. Rats were trained to lever press for cocaine infusions (0.25 mg/kg iv). Some were then tested for cocaine-seeking behavior (i.e., lever presses in the absence of cocaine re-inforcement) immediately following acute 7-OH-DPAT (0.001, 0.01, 0.1, or 1.0 mg/kg sc) or saline administration. Others were tested immediately or 2-23 h following repeated daily 7-OH-DPAT (1.0 mg/kg sc) or saline administration for extinction of cocaine-seeking behavior, cocaine re-instatement of cocaine-seeking behavior, and re-establishment of cocaine self-administration following extinction. 7-OH-DPAT-induced changes in locomotion were also assessed. Cocaine-experienced animals exhibited cross-tolerance to the transient hypoactivity produced by acute 7-OH-DPAT administration. Acute administration of low doses (0.01-0.1 mg/kg) of 7-OH-DPAT attenuated cocaine-seeking behavior, whereas the highest dose (1.0 mg/kg) initially attenuated, then increased, cocaine-seeking behavior. In animals tested immediately following one of the repeated administrations, 7-OH-DPAT did not alter cocaine self-administration, but sensitized locomotion. Repeated 7-OH-DPAT administration also increased cocaine-seeking behavior when administered 0 h, but not 2 or 4 h, before cocaine priming (15 mg/kg ip) and testing. In animals tested 17-23 h following one of the repeated administrations, cocaine-seeking behavior and re-establishment of cocaine self-administration were attenuated, but maintenance of self-administration following re-establishment, cocaine re-instatement of extinguished cocaine-seeking behavior, and spontaneous locomotion were unaltered. The findings suggest that following repeated administration, 7-OH-DPAT produces a transient increase (<2 h) in incentive motivation for cocaine that is followed by a protracted decrease in incentive motivation for cocaine.

Animals↗

PubMed1990

Individual reactivity to novelty predicts probability of amphetamine self-administration.

The present study demonstrates a relationship between individual responses to environmental activation, such as novelty, and propensity to acquire amphetamine self-administration. Locomotor activity cumulated over 2 h of exposure to a circular corridor was a stable and novelty-dependent feature of behaviour in individual rats. The differences between subjects in this behaviour were maintained over two trials at 1 months intervals, but disappeared over 4 days when the animals were tested daily, i.e. when the environment was no longer novel. The subjects with the higher locomotor response to novelty (HR group) also showed a higher propensity to acquire amphetamine self-administration, while the subjects with the lower response to novelty (LR group) did not acquire self-administration over 7 days of testing. Differences in self-administration of HR animals could not be accounted for by differences in exploratory behaviour. Thus, HR animals did not show higher investigative responses in a hole exploration test. Animals with the higher locomotor response to novelty also showed a greater release of corticosterone in the same environment. Since dopaminergic (DA) neurons are activated by both amphetamine and novelty, it is possible that differences in the propensity to acquire amphetamine self-administration may be accounted for by differences in the activity of DA neurons.

Journal Article↗

PubMed1981

Personality factors in human drug self-administration.

By comparing MMPI profiles of sedative-dependent subjects during pentobarbital self-administration with comparable subjects during drug abstinence, the present study has found that self-administration tends to increase rather than decrease indicators of personal distress (MMPI scale scores). This finding agrees fully with other studies of drug effects on mood of drug-dependent subjects. (This finding should disturb only those who equate reinforcement with euphoria and other pleasurable states. Those familiar with the concept of reinforcement understand that reinforcement deals only with behavior and implies nothing about corresponding subjective states). Only scores on the Hypomania scale of the MMPI were found to correlate significantly with amount of daily drug intake, and this relationship occurred primarily in females. Scores on the Depression scale were correlated significantly with the daily pattern of drug-taking behavior. However, in neither case is it known whether the relationship reflects influences of personality factors on drug-taking behavior, or influences of drug-taking behavior on the obtained personality measures. Other research will be needed to answer this question. Clinically depressed individuals may constitute a special sub-group of subjects in which scores on many MMPI scales are related to daily amount of drug intake. Studies of human drug self-administration provide an excellent opportunity for more detailed research into these and other clinical research questions.

Adult↗

PubMed1999

Repeated neonatal maternal separation alters intravenous cocaine self-administration in adult rats.

Behavioural responses to psychostimulant drugs can be profoundly affected by early environmental influences. The aim of this study was to describe the effects of repeated brief separations of rat pups from their dams during the early neonatal period on cocaine self-administration behaviour as adults. Lister hooded rats exposed to a repeated maternal separation procedure (REMS) showed altered acquisition and maintenance of cocaine self-administration as adults, the effects being dose and gender-dependent. Overall, the patterns of acquisition of self-administration across three doses of cocaine (0.05, 0.08 and 0.5 mg/injection) suggested a rightward shift in the acquisition dose-effect functions for the REMS animals relative to control animals. At 0.05 mg/injection, there was a retarded acquisition of cocaine self-administration in male and female neonatally separated rats. At 0.08 mg/injection there was a facilitated acquisition in female neonatally separated subjects. After establishment of stable self-administration of the training dose, in the same cohort of subjects, rightward and downward shifts in the cocaine self-administration dose-effect functions were determined for female and male REMS subjects, respectively, relative to their controls. The dose-effect function for both female groups was shifted to the left of that of the respective male groups, although the lighter body weights of the females meant that they administered a higher unit dose per unit body weight than the males. Whereas male REMS subjects tended to self-administer less cocaine than the controls at the dose eliciting maximal responding (0.03 mg/injection) and to make fewer lever responses overall at each dose tested, female REMS subjects self-administered significantly more cocaine than their respective controls at a dose of 0.03 mg/injection. There was no differential sensitivity to the rate-altering effects of the selective dopamine D2 receptor antagonist, eticlopride, or to the selective dopamine D1 receptor antagonist, SCH 23390. These data provide further evidence that altered early environment affects drug-taking behaviour in a developmentally specific and gender-specific manner, with the effects of neonatal separation contrasting with previously published data on the effects of post-weaning isolation rearing.

Analysis of Variance↗

PubMed1998

Self-administration of cocaine-heroin combinations by rhesus monkeys: antagonism by naltrexone.

Low, nonreinforcing doses of heroin have been shown to shift the dose-response function of cocaine leftward in rhesus monkeys trained under a progressive-ratio schedule of i.v. drug injection. Our study sought to determine 1) whether a reciprocal enhancement of heroin self-administration would be observed when heroin was combined with low, nonreinforcing doses of cocaine, and 2) whether self-administration of cocaine-heroin combinations could be antagonized by the opioid antagonist naltrexone. Rhesus monkeys (n = 4) were prepared with i.v. catheters and trained to self-administer cocaine under a progressive-ratio schedule. The initial response requirement of this schedule was fixed-ratio 120, which doubled across the session to a maximum of 1920. Injections were separated by a 30-min time out. Cocaine dose-response functions (6.4-100 micrograms/kg/injection) for injections/session and breakpoints were monophasic, i.e., increased with dose until responding reached a maximum. Heroin dose-response functions (1.6-25 micrograms/kg/ injection) either increased to a peak and then decreased or reached an asymptote. When nonreinforcing doses of cocaine (3.2-25 micrograms/kg/injection) were combined with heroin, the heroin dose-response function was shifted to the left, without change in maximum injections/session. Pressession treatments with naltrexone (3.2-1600 micrograms/kg, i.m., 10-min presession) antagonized self-administration of heroin and heroin + cocaine combinations in a dose-dependent fashion. However, naltrexone treatment had no effect on cocaine self-administration. Antagonism by naltrexone of self-administration of heroin and heroin + cocaine was surmounted by increasing the dose of heroin either alone or in the heroin + cocaine combination. In vivo apparent pA2 and pKB analyses of these data revealed values of approximately 8.0, consistent with a role for mu opioid receptors in the self-administration of heroin and cocaine-heroin (i.e., "speedball") combinations.

Animals↗

PubMed2003

The GABAB receptor agonists baclofen and CGP44532 decreased nicotine self-administration in the rat.

RATIONALE: Previous work has indicated a potential role for gamma-aminobutyric acid-B (GABA(B)) receptor agonists in treating drug addiction in humans. Specifically, GABA(B) receptor agonists decreased cocaine, heroin and nicotine self-administration in rats. OBJECTIVES: The purpose of the present studies was to extend previous findings by assessing the effects of additional GABA(B) receptor agonists on nicotine self-administration and food-maintained responding, under both fixed and progressive ratio schedules in rats. METHODS: Male Wistar rats were exposed to a progressive ratio schedule where various nicotine doses were made available according to a within-subjects Latin Square design. Additional groups of rats were used to test the effects of the GABA(B) receptor agonists baclofen and CGP44532 on nicotine self-administration (0.01 and 0.03 mg/kg per infusion) and food-reinforced responding on fixed and progressive ratio (CGP44532 only) schedules. RESULTS: Nicotine maintained stable self-administration under a progressive ratio schedule with a linear dose-response function ( r=0.61). Both CGP44532 and (-)baclofen dose-dependently reduced nicotine self-administration on the fixed ratio schedule, and also decreased food-maintained responding at higher doses. Further, CGP44532 decreased breakpoints for nicotine and food at identical doses under the progressive ratio schedule. CONCLUSION: The present data demonstrate that administration of GABA(B) receptor agonists decreased intravenous nicotine self-administration under both fixed and progressive ratio schedules of reinforcement, possibly reflecting reduced rewarding effects of nicotine. Both baclofen and CGP44532 exhibited specificity for nicotine- versus food-maintained responding on the fixed ratio schedules but not on the progressive ratio schedule (CGP44532 tested only), indicating the potential usefulness of GABA(B) receptor agonists as therapeutics for smoking cessation.

Animals↗

PubMed1997

Effects of gamma-aminobutyric acid agonists and N-methyl-D-aspartate antagonists on a multiple schedule of ethanol and saccharin self-administration in rats.

Recently, it has been shown at both the cellular and behavioral levels that ethanol has effects on the N-methyl-D-aspartate (NMDA) and gamma-aminobutyric acid (GABA)a receptor systems, leading to the possibility that the reinforcing effects of ethanol may be, at least partially, mediated via these receptor ionophores. In this study, a multiple schedule of ethanol and saccharin self-administration was used to study that possibility. Adult male Long-Evans rats were trained during 1-hr sessions to press on two different levers for 10% (w/v) ethanol and 0.1% (w/v) saccharin solutions, under an alternating 5-min, fixed-ratio-4 schedule of liquid availability. After training, tests were conducted with ethanol, NMDA antagonists and GABA agonists given before six consecutive sessions. Pretreatment with ethanol selectively decreased ethanol self-administration without altering saccharin self-administration. The competitive NMDA antagonist CPPene (D-3-(2-carboxypiperazine-4-yl)-1-propenyl-1-phosphonic acid [SDZ EAA 494]) and the noncompetitive NMDA antagonist phencyclidine decreased both ethanol and saccharin self-administration. The GABA agonists pentobarbital and diazepam also failed to reduce ethanol self-administration, relative to saccharin. Although these results do not support the hypothesis that antagonism of the NMDA receptor system or activation of the GABA receptor system can selectively modify ethanol-reinforced responding, they identify important issues for designing the best strategies to be used to assess selective drug effects on ethanol self-administration.

Animals↗

PubMed1982

Disruption of cocaine self-administration following 6-hydroxydopamine lesions of the ventral tegmental area in rats.

6-Hydroxydopamine-induced destruction of dopaminergic terminals in the nucleus accumbens have been shown previously to disrupt cocaine and amphetamine self-administration. We sought to determine whether lesions of the DA cell bodies in the ventral tegmental area (VTA) which give rise to the DA innervation of the n. accumbens, would also disrupt cocaine self-administration behavior. Rats were trained to self-inject cocaine (0.75 mg/kg) for 4 hr/day. After a stable baseline was established, one group of rats received bilateral injections of 6-OHDA (4 micrograms/l microliter) into the VTA. Control rats received vehicle injections. When retested on the fifth day post-lesion, all of the 6-OHDA treated animals showed a long lasting reduction in cocaine intake. Three animals did not reinitiate cocaine self-administration after the lesion, although each showed stable post-lesion responding for apomorphine. The surgery had no effect on cocaine self-administration in control animals. These data support the hypothesis that dopaminergic mechanisms are necessary for the normal expression of cocaine self-administration.

Animals↗

PubMed1997

Glucocorticoids and behavioral effects of psychostimulants. II: cocaine intravenous self-administration and reinstatement depend on glucocorticoid levels.

Observations suggest that corticosterone, the principal glucocorticoid hormone in the rat, can modulate the behavioral effects of drugs of abuse. In this report, the influence of corticosterone on intravenous self-administration of cocaine was studied. In the first experiment, cocaine intravenous self-administration in adrenalectomized rats and in adrenalectomized rats receiving corticosterone replacement treatments was studied as a function of corticosterone concentrations and as a function of cocaine doses (0.025, 0.05, 0.1, 0.2, 0.4, 0.8 mg/kg/infusion). In a second experiment, we tested, in intact rats, the effect of different doses of corticosterone (0.09, 0.18, 0.37, 0.58, 0.75 mg/kg) on the reinstatement of an extinguished cocaine self-administration behavior. It is reported that adrenalectomy markedly shifts the cocaine self-administration dose-effect curve downward. This effect was dose-dependently reversed by corticosterone; a complete restoration being obtained for corticosterone levels in the range of those induced by stress. Corticosterone administration also precipitated dose-dependently the reinstatement of cocaine self-administration. The maximal effect was obtained for a dose of corticosterone producing an increase in plasma levels similar to the increase produced by an intense stress. In conclusion, our results show that glucocorticoids facilitate the reinforcing effects of cocaine and support the hypothesis that glucocorticoids are one of the biological factors determining vulnerability to substance abuse.

Animals↗