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PubMed1994

Effects of dopamine on prolactin: interactions with cocaine self-administration by female rhesus monkeys.

The effects of dopamine on regulation of prolactin secretion were studied in female rhesus monkeys before cocaine exposure and again after 2 months to 2.7 years of daily cocaine self-administration. During chronic cocaine exposure, basal prolactin levels increased by 227 to 350% above drug-free control levels (P < .05). On each endocrine study day, three successive 80-min dopamine infusions (10 micrograms/kg/min i.v.) were alternated with 20-min interruptions of dopamine infusions to assess the degree of prolactin suppression and the magnitude of postdopamine prolactin increases. Dopamine significantly reduced prolactin below base-line levels within 60 to 80 min under all conditions (P < .05-.01). In four drug-naive follicular phase females, postdopamine increases in prolactin never exceeded predopamine base-line levels of 6.2 (+/- 1.8) ng/ml. After an average of 74 days of cocaine self-administration [3.7 (+/- 0.11) mg/kg/day], the postdopamine prolactin increases were significantly higher than during drug-free control conditions (P < .01) and reached hyperprolactinemic levels of 57.6 ng/ml. After an average of 300 days of cocaine self-administration [6.5 (+/- 0.06) mg/kg/day], postdopamine prolactin increases peaked at 339% above predopamine basal prolactin levels. After an average of 433 days of cocaine self-administration [6.45 (+/- 0.08) mg/kg/day] postdopamine prolactin increases remained significantly higher (P < .01) than during drug-free conditions. A similar pattern of postdopamine prolactin increases to hyperprolactinemic levels (ranging from 44.5 to 141.2 ng/ml) also were measured in two other females studied after 19 to 20 months of cocaine self-administration [6.21 (+/- 0.11) and 7.49 (+/- 0.17) mg/kg/day]. After 2.7 years of cocaine self-administration, one monkey developed persistent hyperprolactinemia and basal prolactin levels averaged 326 ng/ml after 89 days of cocaine abstinence. These data suggest that the prolactin secretory response to dopamine perturbation may provide a sensitive index of changes in dopaminergic regulation of prolactin during chronic cocaine exposure.

Animals↗

PubMed2006

Corticotropin-releasing factor 1 antagonists selectively reduce ethanol self-administration in ethanol-dependent rats.

BACKGROUND: Alcohol dependence is characterized by excessive alcohol consumption, loss of control over intake, and the presence of a withdrawal syndrome, which includes both motivational and physical symptoms. Similar to human alcoholics, ethanol-dependent animals display enhanced anxiety-like behaviors and enhanced ethanol self-administration during withdrawal, effects hypothesized to result from a dysregulation of corticotropin-releasing factor (CRF) stress systems. Here, we used an animal model of ethanol dependence to test the effects of CRF(1) receptor antagonists on excessive ethanol self-administration in dependent rats. METHODS: Wistar rats, trained to orally self-administer ethanol, were exposed intermittently to ethanol vapors to induce ethanol dependence. Nondependent animals were exposed to control air. Following a 2-hour period of withdrawal, dependent and nondependent animals were systemically administered antalarmin, MJL-1-109-2, or R121919 (CRF(1) antagonists) and ethanol self-administration was measured. RESULTS: The nonpeptide, small molecule CRF(1) antagonists selectively reduced excessive self-administration of ethanol in dependent animals during acute withdrawal. The antagonists had no effect on ethanol self-administration in nondependent rats. CONCLUSIONS: These data demonstrate that CRF(1) receptors play an important role in mediating excessive ethanol self-administration in dependent rats, with no effect in nondependent rats. CRF(1) antagonists may be exciting new pharmacotherapeutic targets for the treatment of alcoholism in humans.

Alcoholism↗

PubMed1989

Chlordiazepoxide alters intravenous cocaine self-administration in rats.

This investigation was designed to examine the effects of benzodiazepines on intravenous cocaine self-administration in rats. Pretreatment with low doses of the benzodiazepine receptor agonist, chlordiazepoxide (0.3 to 1.0 mg/kg, IP), resulted in small but nonsignificant increases in drug intake with 0.5 mg/kg cocaine, while higher doses (10 mg/kg, IP) significantly decreased drug intake in all rats tested. The effects of chlordiazepoxide on self-administration were attenuated when the concentration of cocaine was increased to 1.0 mg/kg, suggesting that chlordiazepoxide was opposing rather than augmenting the pharmacological actions of cocaine. Pretreatment with the benzodiazepine receptor antagonist, Ro 15-1788 (1.0 to 10 mg/kg, IP), had no effect on self-administration, suggesting that the reinforcing properties of cocaine do not result from direct interactions with benzodiazepine receptors. The result of this investigation demonstrate that chlordiazepoxide alters intravenous cocaine self-administration in rats. Although additional research will be necessary to confirm these data, the results of this investigation suggest that chlordiazepoxide may decrease the reinforcing efficacy of cocaine through indirect actions on dopaminergic neuronal activity potentially mediated through GABAergic mechanisms via benzodiazepine receptor activation.

Animals↗

PubMed1989

Differential effects of the pharmacological manipulation of serotonin systems on cocaine and amphetamine self-administration in rats.

The effects of the administration of serotonergic drugs on infusion rates of rats self-administering cocaine and amphetamine on an FR-10 schedule of reinforcement in daily 4 hour sessions were compared. Pretreatment with fluoxetine (2.5, 5, and 10 mg/kg), an inhibitor of serotonin reuptake, significantly decreased rates of responding maintained by amphetamine, but had no effect on responding maintained by cocaine at any of the doses tested. Pretreatment with cinanserin (3, 10, and 17.5 mg/kg), a serotonergic receptor antagonist, decreased rates of amphetamine self-administration at the highest dose tested, and also had no effect on cocaine self-administration. These data suggest a differential sensitivity of cocaine and amphetamine self-administration to pharmacological manipulation of central serotonin systems. They are consistent with biochemical data which demonstrates a negative correlation between the reinforcing potency of amphetamine-like drugs, but not cocaine-like drugs and their potency at serotonin binding sites.

Amphetamine↗

PubMed1997

Acquisition and maintenance of intravenous cocaine self-administration in Lewis and Fischer inbred rat strains.

Lewis and Fischer inbred rat strains differ in behavioral and biochemical responses to psychoactive drugs: Lewis rats show greater behavioral responses to psychoactive drugs than Fischer rats and they fail to show biochemical adaptations in the mesolimbic dopamine system after chronic drug exposure, in contrast to Fischer and outbred rats. This suggests that Fischer and Lewis rats may differ in the initial, reinforcing effects of psychoactive drugs, but not in responses seen after the exposure that occurs with maintenance of drug-reinforced behavior. Thus, the present study tested whether these strains differ in acquisition or maintenance of intravenous cocaine self-administration. Acquisition of cocaine self-administration was examined in separate groups that were allowed 15 days to acquire the operant at one of three cocaine doses (0.25, 0.5, or 1.0 mg/kg/infusion). Compared to Fischer rats, Lewis rats acquired cocaine self-administration after fewer training trials and at lower doses. After maintenance, both strains showed characteristic extinction responding with saline substitution and dose-related responding to cocaine, although Fischer rats tended to show higher response rates. Finally, cocaine plasma levels, obtained after an intravenous cocaine infusion (1.0 mg/kg), showed no strain differences suggesting that the strain difference in acquisition was not due to cocaine pharmacokinetics. These strain differences in acquisition of cocaine self-administration may be related to reported strain differences in the mesolimbic dopamine system. Further, because acquisition of drug self-administration is an animal model of vulnerability to drug addiction, these inbred strains may be useful to study factors underlying such vulnerability.

Animals↗

PubMed2005

Reduced cocaine self-administration in muscarinic M5 acetylcholine receptor-deficient mice.

The reinforcing effects of cocaine have been related to increased extracellular concentrations of dopamine in the ventral striatum. Several studies suggest that M5 muscarinic receptors facilitate striatal dopamine release. We tested the hypothesis that the reinforcing effects of cocaine are decreased in M5 receptor-deficient mice using chronic intravenous cocaine self-administration in extensively backcrossed mice. We also assessed whether operant performance generally, rather than cocaine self-administration specifically, was altered in the mutant mice. To this end, we evaluated both food-maintained operant behavior and cocaine self-administration under a fixed ratio 1 and a progressive ratio (PR) schedule of reinforcement. We also evaluated acquisition of self-administration in experimentally naive mice using several doses of cocaine. M5 receptor deletion decreased self-administration of low to moderate doses of cocaine under a PR schedule of reinforcement and diminished acquisition of self-administration of a low dose in experimentally naive mice. We found no differences between genotypes in food-maintained behavior. The present study extends our previous findings using backcrossed mice and covering various experimental conditions. Our results indicate that M5 receptor deletion diminished the reinforcing effects of low doses of cocaine and identified specific conditions under which this may be observed.

Aggression↗

PubMed2001

The GABA(B) antagonist CGP56433A attenuates the effect of baclofen on cocaine but not heroin self-administration in the rat.

RATIONALE: Several reports have demonstrated that the gamma-aminobutyric acid (GABA)(B) agonist baclofen attenuates the reinforcing effects of cocaine in rats, and recent evidence indicates that it might have a similar effect on heroin self-administration. OBJECTIVES: The specific GABA(B) receptor antagonist CGP56433A was used to further evaluate the involvement of GABA(B) receptors in the baclofen-induced suppression of cocaine and heroin self-administration. METHODS: In the first series of experiments, dose-response curves were generated to examine the effect of CGP56433A (0.6, 1.0, or 1.8 mg/kg, i.p.) on cocaine (1.5 mg/kg per injection) and heroin (25 microg/kg per injection) self-administration reinforced under a fixed-ratio (FR1) or progressive ratio (PR) schedule. Separate sets of experiments then examined the effect of the co-administration of CGP56433A and baclofen on responding for cocaine or heroin under both schedules. RESULTS: Pretreatment with CGP56433A had no effect on cocaine or heroin self-administration, while baclofen dose dependently reduced responding for both cocaine and heroin under both the FR1 and PR schedule. CGP56433A (1.8 mg/kg) blocked the effect of baclofen on cocaine but not on heroin self-administration. CONCLUSION: The specific GABA(B) antagonist CGP56433A attenuated the effect of baclofen on cocaine self-administration, suggesting that GABA(B) receptors are critical in mediating the anti-cocaine effect of baclofen. In combination with other studies, the data demonstrate that the susceptibility of baclofen and other GABA(B) agonists to receptor blockade depends on the behavioral response being studied. Whether this indicates different receptor mechanisms are involved (e.g., pre- versus post-synaptic effects or differential receptor reserve) remains to be determined.

Animals↗

PubMed2006

Effects of central neurokinin-1 receptor antagonism on cocaine- and opiate-induced locomotor activity and self-administration behaviour in rats.

The neuropeptide substance P (SP) and its preferred receptor, the neurokinin-1 (NK-1) receptor, have been implicated in some of the reward-related behavioural effects of abused drugs, including psychostimulants and opiates. The first objective of the present series of experiments was to assess the role of the NK-1 receptor in two reward-related behavioural effects of cocaine: locomotor activity and self-administration. In tests for locomotor activity, rats were given intracerebroventricular (ICV) infusions of the selective NK-1 receptor antagonist, GR82334 (0, 10, 50 pmol), prior to systemic injections of cocaine. In self-administration experiments, rats were trained to self-administer cocaine on a fixed-ratio 5 (FR5) schedule of reinforcement. Following acquisition of stable responding, animals were pretreated with GR82334 (0, 2, 10, 50 pmol; ICV) prior to subsequent self-administration sessions. Based on evidence suggesting a potentially selective role for NK-1 receptors in opiate reward, we also examined the effects of GR82334 on morphine-induced locomotor activity and heroin self-administration. Results showed that GR82334 had no effect on cocaine-induced locomotor activity or cocaine self-administration, but attenuated morphine-induced locomotor activity and increased heroin self-administration. These findings suggest that endogenous activity at NK-1 receptors may play a specific role in opiate-induced, but not cocaine-induced, locomotor activation and reinforcement.

Animals↗

PubMedDate not supplied

Pharmacology of drug self-administration.

Limited access to drugs provides a reliable model for their acute-reinforcing effects and a means by which to explore neuropharmacological mechanisms involved in these effects. In limited access situations intravenous self-administration rates of opiates and psychomotor stimulants is inversely related to dose, and competitive antagonists at low doses increase the number of injections self-administered. Competitive agonists decrease drug self-administration. However noncompetitive antagonists tend to produce decreases in self-administration and the specificity of these results are difficult to interpret. A limited access procedure of ethanol (10% v/v) self-administration using a sucrose or saccharin fade out procedure resulted in reliable and stable ethanol (10% v/v) and water self-administration in a concurrent choice situation using nondeprived unselected Wistar and alcohol preferring P-rats. As observed by others, the opiate antagonist naloxone decreased fluid intake in both strain of rats. However, contrary to earlier results naloxone did not produce a selective decrease in ethanol preference. The serotonin antagonist methysergide had no significant effect on fluid intake or ethanol preference. However, the long-acting dopamine agonist bromocriptine decreased ethanol intake and increased water intake producing a significant decrease in ethanol preference. The results with naloxone suggest that opiate interactions with ethanol may reflect a more general effect on consummatory behavior and the results with bromocriptine suggest that the reinforcing effects of low doses of ethanol may involve a dopaminergic component. Future studies should explore further the interactions of ethanol with competitive antagonists (if possible), and fluid intake or ethanol preference with limbic-extrapyramidal circuitry involved in mediating the reinforcing actions of other drugs of abuse.

Animals↗

PubMed2002

Intravenous cocaine and heroin self-administration in rats selectively bred for differential saccharin intake: phenotype and sex differences.

RATIONALE: Rats selectively bred for high intake of a sweet saccharin solution (HiS) consume more ethanol than their low-saccharin intake (LoS) counterparts. The HiS phenotype may be a predictor of abuse of other drugs via other routes of administration. OBJECTIVE: HiS and LoS, male and female rats were tested for acquisition of IV cocaine and heroin self-administration under a fixed-ratio 1 (FR1) schedule, and cocaine-reinforced behavior was examined under a progressive-ratio (PR) schedule. METHODS: Four groups of rats (HiS males and females and LoS males and females) were trained to self-administer IV cocaine (0.2 mg/kg), and another four groups were trained to self-administer heroin (0.015 mg/kg) using an automated autoshaping procedure. Rats were allowed 30 days to reach a criterion whereby a mean of 100 (cocaine) or 20 (heroin) infusions were self-administered during 6-h sessions over 5 consecutive days. RESULTS: The HiS female rats acquired cocaine self-administration significantly more rapidly than the LoS rats, and females of both phenotypes met the acquisition criteria more rapidly than males. In both HiS and LoS cocaine groups a greater percentage of females (compared with males) met the acquisition criteria within 30 days. The only cocaine group in which 100% met the criterion was the HiS females. The female (compared with male) heroin groups showed a more rapid rate of acquisition, but there was no difference due to saccharin phenotype. In each of the four heroin groups 100% of all rats met the criteria within 30 days. Results of the PR schedule in the HiS females and males and LoS females indicated significantly higher break points in the HiS females (compared with HiS males), but there were no differences in females due to phenotype. CONCLUSION: Female rats selectively bred for higher saccharin intake show more rapid and successful acquisition of IV self-administration of a low dose of cocaine than those bred for low saccharin intake. Female rats (compared with males) consistently showed accelerated rates of acquisition and maintenance (PR) of cocaine self-administration and acquisition of heroin self-administration.

Analysis of Variance↗

PubMed2005

Attentional and motivational deficits in rats withdrawn from intravenous self-administration of cocaine or heroin.

RATIONALE: Identifying the long-term neurocognitive sequelae of drug addiction may have important implications for understanding the compulsive, chronically relapsing nature of this brain disorder. OBJECTIVES: Our aim was to investigate the consequences of chronic intravenous self-administration of cocaine or heroin on visual attentional processes in rats. METHODS: Adult male rats were pretrained on a five-choice serial reaction time task (5-CSRTT) of sustained visual attention and impulsivity and later trained to self-administer cocaine or heroin intravenously during multiple 'long-access' self-administration cycles. Control rats had identical training and surgical experience, but received passive infusions of saline during self-administration sessions. Executive cognitive processes of selection and inhibitory response control were evaluated 24 h after drug discontinuation and for a further 6 days prior to the next cycle of self-administration. RESULTS: Findings indicate similar behavioural disturbances on the five-choice task in cocaine- and heroin-withdrawn rats with significantly impaired attentional accuracy, increased omissions and slower latencies to respond correctly during the early, but not late, withdrawal period. The self-administration of either drug was not associated with significant alterations in impulsive actions, and there was no evidence of persistent alterations in visual attentional performance. However, unlike rats self-administering cocaine, the motivation to collect food reward on the 5-CSRTT was significantly reduced in heroin-withdrawn animals for a period of at least 6 weeks. CONCLUSIONS: These data, together with recent findings of attentional dysfunction during the withdrawal of intravenous self-administration of amphetamine, suggest that generically different drugs of abuse produce similar disturbances in visual attentional performance during the early withdrawal period.

Analgesics↗

PubMed2005

Abstinence from cocaine self-administration heightens neural encoding of goal-directed behaviors in the accumbens.

Cocaine addiction in humans is characterized by cycles of abstinence from drug-taking and relapse. Here, electrophysiological recording procedures were used to determine whether nucleus accumbens (Acb) neuronal firing properties are altered following interruption and resumption of cocaine self-administration. Rats (n = 12) were trained to self-administer cocaine (2 h daily sessions) then divided into two groups. Acb activity was recorded for Group 1 (controls) during two additional self-administration sessions completed over the next 2 days (test sessions 1 and 2). Acb activity was recorded for Group 2 (1-month) during one self-administration session completed the next day (test 1), and during a second self-administration session 1 month later (test 2). As in prior reports, a subset of Acb neurons exhibited patterned discharges (short duration and/or long-term cyclic alterations, termed 'phasically active') relative to cocaine-reinforced responding during test session 1. Remarkably, the percentage of phasically active cells dramatically increased (nearly two-fold) following 1-month abstinence, in the core but not the shell of the Acb. Likewise, the strength of the neural correlates (determined via signal-to-baseline ratios) also increased as a function of abstinence. Extinction experiments in another set of rats (n = 12) revealed an increased motivational state for the drug following abstinence. The results show that abstinence from cocaine self-administration causes a dramatic increase in the number and strength of Acb neurons that encode cocaine-related information, thus representing the first neurophysiological correlate of heightened activation of the 'brain reward system' following abstinence and resumption (relapse) of cocaine consumption.

Action Potentials↗

PubMed2004

Gabapentin maintenance decreases smoked cocaine-related subjective effects, but not self-administration by humans.

Data from research with laboratory animals indicate that cocaine self-administration can be reduced by lambda-aminobutyric acid (GABA) agonists. Yet, the effectiveness of GABA agonists to decrease human cocaine self-administration has not been investigated under controlled laboratory conditions. The purpose of this study was to assess the effects of gabapentin, a GABA agonist, on cocaine-related behaviors, including self-administration, in human research participants under controlled laboratory conditions. During this 48-day double-blind, crossover design study, the effects of gabapentin (0, 600, and 1200 mg/d) maintenance on response to cocaine (0, 12, 25, and 50 mg) were investigated in seven cocaine abusers. Active cocaine significantly increased choice to self-administer cocaine, subjective-effect ratings (e.g., "Good Drug Effect"), blood pressure and heart rate (HR). Gabapentin did not reduce cocaine choice or cardiovascular measures, but it did decrease some subjective effects of cocaine (e.g., "Good Drug Effect" and "Anxious"). These data suggest that the cocaine-gabapentin combination was well-tolerated, and because some cocaine-related subjective effects were reduced by maintenance on relatively low gabapentin doses, future studies should test higher gabapentin doses.

Acetates↗

PubMed1997

Increased aggression after ethanol self-administration in male resident rats.

In order to study experimental alcohol intake that leads to heightened aggression, we established ethanol self-administration in aggressive rats. The focus was on low doses of self-administered ethanol and to assess their effects on aggressive behavior in resident rats, using a limited access paradigm followed by a 5-min confrontation with an intruder. In the first phase of the experiment, rats were established as "residents", and their consistent aggressive behavior in confrontations with an intruder was verified. In the second phase, these resident rats were trained to self-administer alcohol, using a sucrose-fading technique. In the third phase, alcohol self-administration was followed by intruder confrontations in order to study the effect of alcohol on aggression. Confrontations after ethanol consumption leading to low (5-20 mg/dl) and moderate (20-50 mg/dl) blood alcohol concentration (BAC) were compared to confrontations without alcohol, each animal serving as its own control. On average, the group showed no change in aggressive behavior after low or moderate ethanol intake. However, six out of 16 individuals significantly increased the number of attack bites and the duration of aggressive behavior by up to 90% after alcohol self-administration. When these rats were assigned post-hoc to an alcohol heightened aggression group, the group was characterized by a 40% increase in number of attack bites and a 90% increase in aggressive posture over control (BAC 0 mg/dl), whereas the alcohol non-heightened aggression group showed no significant changes. These results extend previous observations of increased aggression in a subpopulation of animals after experimenter-administered ethanol in mice, rats and monkeys to self-administered alcohol. Using this animal model, individuals showing enhanced or reduced aggression after oral alcohol self-administration can be characterized behaviorally, physiologically, and neurochemically.

Aggression↗

PubMed2006

18-Methoxycoronaridine acts in the medial habenula and/or interpeduncular nucleus to decrease morphine self-administration in rats.

The novel iboga alkaloid congener 18-methoxycoronaridine (18-MC) is a putative anti-addictive agent that has been shown, in rats, to decrease the self-administration of morphine and other drugs of abuse. Previous work has established that 18-MC is a potent antagonist at alpha3beta4 nicotinic receptors. Because alpha3beta4 nicotinic receptors in the brain are preferentially located in the medial habenula and the interpeduncular nucleus, the present study was conducted to determine if 18-MC could act in these brain areas to modulate morphine self-administration in rats. Local administration of 18-MC into either the medial habenula or the interpeduncular area decreased morphine self-administration while having no effect on responding for a non-drug reinforcer (sucrose). Similar results were produced by local administration into the same brain areas of two other alpha3beta4 nicotinic antagonists, mecamylamine and alpha-conotoxin AuIB. Local administration of 18-MC into the ventral tegmental area had no effect on morphine self-administration. These and other data are consistent with the hypothesis that 18-MC decreases morphine self-administration by blocking alpha3beta4 nicotinic receptors in the habenulo-interpeduncular pathway.

Animals↗

PubMed2005

The serotonin/noradrenaline reuptake inhibitor venlafaxine attenuates acquisition, but not maintenance, of intravenous self-administration of heroin in rats.

Opioids and antidepressants are frequently used for the treatment of various pain conditions. A combination of both drug classes may be more effective than either treatment alone, and combined treatment with an antidepressant may result in an opiate-sparing effect. Although it has been shown that antidepressants can attenuate self-administration of psychomotor stimulant and depressant drugs, it is not known whether they also attenuate self-administration of opiates. To determine whether venlafaxine, a serotonin/noradrenaline reuptake inhibitor with antidepressive and analgesic properties, affects acquisition and maintenance of intravenous heroin self-administration in rats, male Long-Evans rats were trained to press a lever in order to receive heroin (0.05 mg/kg/infusion) under a fixed ratio or a progressive ratio schedule. A control group was trained in a fixed ratio food-reinforced operant procedure. The effect of venlafaxine on operant responding for heroin and food was assessed both during acquisition and, in separate groups of rats, during maintenance (i.e., after acquisition) of self-administration behaviour. Daily treatment with venlafaxine (10 mg/kg i.p.) before the operant session attenuated the acquisition of responding for heroin, but not for food. However, when tested during the maintenance phase in rats showing stable responding, acute treatment with venlafaxine only marginally affected operant responding for heroin under a fixed ratio:10 schedule of reinforcement, and neither acute nor subchronic (once daily during 4 weeks) venlafaxine treatment affected responding under a progressive ratio schedule. Thus, daily treatment with an antidepressant attenuates the acquisition of heroin self-administration in a behaviourally specific manner, while having only marginal effects on maintenance of heroin self-administration.

Animals↗

PubMed1995

Social stress increases the acquisition of cocaine self-administration in male and female rats.

The effect of social stress on the vulnerability to commence cocaine self-administration was examined in Sprague-Dawley rats repeatedly exposed to aggressive attack by a same-sex opponent. Both sexes were studied, since the factors influencing the acquisition of drug self-administration in females have not been defined. Male and female rats encountered an aggressive male or lactating female opponent on four separate occasions over the course of one week. Control male and female rats were not exposed to attack. All animals were implanted with jugular catheters, and six days later placed into the self-administration box, where a nose-poke in the designated 'active hole' resulted in a 20 microliters injection of cocaine (0.32 mg/kg). Nose-pokes in an 'inactive' hole had no effect. Male and female rats that had experienced social stress self-administered more cocaine than non-defeated controls. The difference between the stressed and non-stressed animals in the number of cocaine injections was not present during the first few days of exposure to cocaine, but became more pronounced over time. Social stress increased the number of responses for cocaine, but did not alter the number of non-specific responses. Sex differences in self-administration were not significant. Therefore, social status appears to be a potent influence in the onset of drug taking behavior in both male and female rats.

Aggression↗

PubMed2002

Sex differences in the effects of baclofen on the acquisition of intravenous cocaine self-administration in rats.

Baclofen, a GABA(B) agonist, decreases both the maintenance and reinstatement of i.v. cocaine-reinforced responding in rats. In the present experiment the effects of baclofen were extended to a comparison of male and female rats during the acquisition of i.v. cocaine self-administration. Four groups of rats were trained to self-administer i.v. cocaine (0.2 mg/kg) under a fixed-ratio 1 (FR 1) schedule using an autoshaping procedure. The criterion for acquisition was a 5-day period during which a mean of 100 cocaine infusions were administered. Rats were given 30 days to reach this criterion. Male and female groups (n=10-13) were pretreated with i.p. injections of baclofen (2.5 mg/kg) or vehicle 30-min prior to the sessions. A subset of rats (N=5) that did not acquire cocaine self-administration continued to be exposed to the acquisition procedure after baclofen treatment ended. Pretreatment with baclofen decreased both the rate of acquisition of cocaine self-administration and the percentage of rats meeting the acquisition criterion to a greater extent in females than in males. Female rats that did not meet the acquisition criterion with baclofen treatment, acquired within a few days after treatment ended. The findings confirm previous reports of enhanced acquisition of cocaine self-administration in females versus males, and they indicate that baclofen suppressed the acquisition of cocaine self-administration significantly more in females than in males.

Animals↗