Effects of voluntary exercise and sex on multiply-triggered heroin reinstatement in male and female rats.

BACKGROUND: The rise in heroin addiction has heightened the need for novel and effective treatments. Physical exercise has been shown as an effective treatment for stimulant abuse in clinical and pre-clinical research. However, this treatment has not yet been tested on opioid addiction. This study examined the effects of physical activity (wheel running) on heroin-seeking in rats within a reinstatement paradigm (i.e., heroin relapse model). METHODS: Female and male rats were trained to self-administer intravenous heroin (0.015 mg/kg). Once trained, rats were placed into extinction (i.e., heroin abstinence) for 21 days with continuous access to a locked or unlocked running wheel. After extinction, rats were tested for drug- (heroin, caffeine, and yohimbine) and cue-primed reinstatement of heroin-seeking. RESULTS: Females completed more wheel revolutions than males across all study phases. Access to an unlocked running wheel reduced extinction and reinstatement of heroin-seeking, with greater reductions in females than males across several reinstatement conditions. In the locked wheel group, female rats showed greater reinstatement of heroin-seeking than males across several priming conditions. CONCLUSIONS: Wheel running reduced heroin-seeking in male and female rats, with females showing a more robust effect during reinstatement. The locked wheel group allowed an examination of sex differences in heroin reinstatement, which revealed that females showed greater vulnerability to heroin reinstatement than males, but with no other sex differences observed in maintenance or extinction. Overall, the results indicate that voluntary physical exercise may be an effective treatment for heroin dependence in humans.

Food deprivation increases oral and intravenous drug intake in rats.

Rats given continuous access to etonitazene hydrochloride in their drinking water (5 micrograms per milliliter) more than doubled their drug intake while deprived of food. Another group of rats with implanted jugular catheters self-administered etonitazene (10 micrograms per kilogram) intravenously on a continuous reinforcement schedule, and the number of infusions increased significantly on days when they were deprived of food. These results suggest that feeding condition may be a powerful determinant of drug-reinforced behavior.

Antihistamines block radiation-induced taste aversions.

When rats are treated with an antihistamine prior to being given sublethal doses of ionizing radiation, the formation of a conditioned saccharin aversion is completely inhibited. A profound aversion could be conditioned with histamine diphosphate as the aversive stimulus. The increase in histamine production after radiation exposure represents the physiological basis of radiation-induced taste aversions.

An uncommon ankle sprain.

OBJECTIVE: Ankle sprain is the most frequently occurring acute injury in tennis, accounting for 20-25% of all injuries. In the current paper, we assess the cause of ankle sprain and suggest possibilities to be considered during diagnosis. METHODS: We assessed a professional tennis player with a partial tear of the long peroneal tendon after an ankle sprain by physical exam, X-ray and MRI. RESULTS: Conservative treatment by means of soft cast and propriocepsis training led to full recovery. CONCLUSION: Peroneal tendon disorders must be part of the differential diagnosis after ankle sprain in the professional athlete.

Cocaine self-administration and reinstatement in female rats selectively bred for high and low voluntary running.

BACKGROUND: Previous research has found that rats behaviorally screened for high (vs. low) wheel running were more vulnerable to cocaine abuse. To assess the extent to which a genetic component is involved in this drug-abuse vulnerability, rats selectively bred for high or low voluntary running (HVR or LVR, respectively) were examined for differences in cocaine seeking in the present study. METHODS: Female rats were trained to lever press for food and then were assessed for differences in acquisition of cocaine (0.4mg/kg; i.v.) self-administration across 10 sessions. Once acquired, rats self-administered cocaine for a 14-day maintenance phase, followed by a 14-day extinction phase when cocaine was no longer available. Subsequently, reinstatement of cocaine seeking was examined with priming injections of cocaine (5, 10 & 15mg/kg), caffeine (30mg/kg), yohimbine (2.5mg/kg) and cocaine-paired cues. RESULTS: A greater percentage of LVR rats met the acquisition criteria for cocaine self-administration and in fewer sessions than HVR rats. No differences in responding for cocaine were observed between phenotypes during maintenance. However, during extinction LVR rats initially responded at higher rates and persisted in cocaine seeking for a greater number of sessions. No phenotype differences were observed following drug and cue-primed reinstatement of cocaine seeking. CONCLUSIONS: In general, LVR rats were more sensitive to the reinforcing effects of cocaine than HVR rats during periods of transition into and out of cocaine self-administration. Thus, LVR rats sometimes showed a greater vulnerability cocaine seeking than HVR rats.

Self-administration of orally-delivered phencyclidine and ethanol under concurrent fixed-ratio schedules in rhesus monkeys.

Five monkeys were trained to self-administer orally-delivered phencyclidine (0.25 mg/ml) and water under concurrent fixed-ratio 16 (FR 16) schedules during daily sessions that lasted 3 h. An 8% (w/v) ethanol solution was substituted for water and then the following series of phencyclidine concentrations was presented: 0.25, 0.5, 1, 0.03, 0.06, 0.12, 0 (water), and 0.25 mg/ml (retest). Next, the phencyclidine concentration was held constant (0.25 mg/ml), and the ethanol concentration was varied as follows: 8, 16, 32, 1, 2, 4, 0 (water), and 8% w/v (retest). Each drug concentration series was tested again with water concurrently available. At low phencyclidine concentrations the ethanol solution was preferred, but phencyclidine deliveries exceeded ethanol deliveries at higher phencyclidine concentrations. Ethanol-maintained responding was increased by the lower phencyclidine concentrations (0.03, 0.06 and 0.12 mg/ml), and it was slightly suppressed by the highest concentration (1 mg/ml). Phencyclidine was preferred to all concentrations of ethanol except 4%. Ethanol (8%) suppressed phencyclidine-maintained behavior at lower concentrations, but it had no effect at higher phencyclidine concentrations. The ethanol concentration-response functions were nearly identical whether phencyclidine (0.25 mg/ml) or water was concurrently present. Drug preferences were usually evident within the first 10 min of the session, suggesting they were based on olfaction, taste, or other immediate postingestional effects. These results show that two orally-delivered drugs may be concurrently self-administered under independently-operating FR schedules. Behavior maintained by one drug depends on the magnitude of the concurrently available, alternative reinforcing drug.

Oral self-administration of phencyclidine analogs by rhesus monkeys: conditioned taste and visual reinforcers.

Three monkeys self-administered orally-delivered phencyclidine, 1-(1-phencyclohexyl) piperidine (PCP), N-ethyl-1-phencyclohexylamine (PCE), and 1-[1-(2-thienyl)cyclohexyl]piperidine (TCP) over a wide range of concentrations (0.0156, 0.0312, 0.0625, 0.125, 0.25, and 0.5 mg/ml). Water was also available under a concurrent fixed-ratio (FR) 16 schedule. Drug deliveries were substantially higher than concurrent water deliveries at all concentrations, indicating that the three compounds functioned as effective reinforcers. Maximum liquid deliveries occurred at concentrations of 0.0625 (PCP and TCP) and 0.125 mg/ml (PCE). TCP was much shorter-acting (10-15 min) than PCP (4-6h) based on observations of severe ataxia at high concentrations. To investigate the conditioned reinforcing effects of taste, a quinine solution (0.088 mg/ml) was substituted for PCP (0.25 mg/ml) in five monkeys. Four monkeys responded for quinine in excess of water for a range of seven to over 30 sessions, while one monkey (M-R) did not show any substantial responding for quinine. With the same five monkeys (treatment order mixed), the effect of visual stimuli was tested by substituting water for PCP while retaining the visual stimuli indicating drug availability. Four monkeys showed increased responding on the side signaling drug for only 0-4 sessions, while one monkey (M-R) showed persistent responding for water on the side with drug stimuli for 29 sessions. These results indicated that taste functioned as an effective conditioned reinforcer, while visual stimuli appeared to be less effective in the oral drug self-administration paradigm.

Reinstatement of cocaine self-administration in rats: sex differences.

RATIONALE: Results obtained with both humans and animals suggest that rates of relapse, or levels of reinstatement responding, may differ between males and females. However, the results obtained with humans are equivocal, and few studies have compared male and female animals on reinstatement responding. OBJECTIVES: The present experiment was designed to compare male (n=8) and female (n=8) rats on reinstatement of extinguished cocaine-reinforced responding. METHODS: Reinstatement of responding was examined using a priming model in which lever pressing for cocaine (0.2 mg/kg) was extinguished by replacing cocaine infusions (2 h) with saline infusions (5 h). After responding extinguished during hour 3, reinstatement of responding was tested by administering one of several priming injections of cocaine (0.32, 1.0 and 3.2 mg/kg) or an equal volume of saline. RESULTS: Although males and females did not differ in the number of saline infusions self-administered after either saline or 0.32 mg/kg cocaine-priming injections, female rats self-administered significantly more saline infusions than males after 1.0 mg/kg and 3.2 mg/kg cocaine-priming injections. Additionally, the effects of 0.32 mg/kg cocaine-priming injections were significantly different from those of saline-priming injections for female, but not male, rats. There was no significant difference between males and females in total cocaine self-administered during hours 1 and 2. CONCLUSIONS: These findings indicate that female rats are more sensitive than males during the reinstatement phase of drug abuse.

Acquisition of i.v. amphetamine and cocaine self-administration in rats as a function of dose.

The effect of dose on the acquisition of i.v. amphetamine and cocaine self-administration was examined. Three unit doses of amphetamine (0.03, 0.06 and 0.12 mg/kg) and three unit doses of cocaine (0.05, 0.2 and 0.8 mg/kg) were tested in separate groups of ten (amphetamine) or 13 (cocaine) rats. Autoshaping methods were used to train rats to press a lever that resulted in drug infusion under a fixed-ratio (FR) 1 schedule. A daily 6-h autoshaping component non-contingently delivered 60 infusions according to a 60-s random time schedule with ten infusions delivered during the first half of each h. Each day autoshaping sessions were followed by a 6-h self-administration session. The criterion for acquisition was a 5-day period during which a daily mean of 100, 50 or 25 infusions for the three amphetamine doses and 400, 100 or 25 infusions were earned during the 6-h self-administration period for the three cocaine doses, respectively. As dose increased, more rats per group acquired drug self-administration and the mean number of days to meet the acquisition criterion decreased. The percentage of rats acquiring amphetamine self-administration increased with dose and ranged from 80 to 100%. Only one rat at the lowest cocaine dose met the acquisition criterion, but 100 percent of the rats at the two higher doses acquired. During the last 2 days of acquisition, mean infusions decreased and mean drug intake (mg/kg) increased as dose increased. On the last day of acquisition, the time course of infusions during the 6-h self-administration component was characterized by a steady rate of infusions per hour, and number of infusions was inversely related to dose. These findings indicate that the initial available dose of a drug is an important determinant of the rate and probability that successful acquisition will occur.

Increased phencyclidine self-administration due to food deprivation: interaction with concentration and training conditions.

Six monkeys were trained to self-administer orally delivered phencyclidine (0.25 mg/ml) under a fixed-ratio 16 (FR-16) schedule. Water was concurrently available under an FF-16 schedule. During initial phencyclidine training, three monkeys were allowed free access to food (food satiation) and three were maintained at 85% of their free-feeding body weights (food deprivation). At the end of the training phase, the food-satiated monkeys were food-deprived. After behavior was stable for ten sessions, all monkeys were food-satiated and tested with a range of phencyclidine concentrations (0.0625-1 mg/ml). They were subsequently food-deprived and tested with concentrations of 0.0312-1 mg/ml, and then they were again food-satiated and tested with 0.0312 and 0.25 mg/ml. The monkeys that were trained to self-administer phencyclidine while food-satiated showed substantial phencyclidine-maintained responding at lower drug concentrations when later tested while food-satiated. In contrast, monkeys that were trained while food-deprived did not respond for phencyclidine in excess of water at the lower concentrations when later tested while food-satiated. Drug-maintained performance during food deprivation did not change systematically as a function of training condition (food deprivation versus food satiation). These results illustrated a marked interaction between drug concentration and the feeding condition and this interaction was modified by training history.

Effects of buprenorphine on self-administration of cocaine and a nondrug reinforcer in rats.

Nine groups of rats self-administered intravenously-delivered cocaine (0.1, 0.2, or 0.4 mg/kg) during 24-h sessions contingent upon lever-press responses under a fixed-ratio (FR) 4 schedule. Three other groups of rats responded on tongue-operated drinking devices for deliveries (0.01 ml) of a solution of glucose and saccharin (G + S). There were an additional three groups that initially self-administered cocaine (0.2 mg/kg), and later saline replaced cocaine and extinction behavior was allowed to stabilize. All 15 groups of rats were injected twice daily for 5 days with one of three doses of buprenorphine (0.1, 0.2 or 0.4 mg/kg). Buprenorphine decreased cocaine self-administration, but the effect of the highest dose was only slightly greater than that of the lowest dose tested. Cocaine infusions were reduced on the first day of treatment, but they increased over the next 4 days of buprenorphine injections. Buprenorphine decreased G + S intake during the last 2 or 3 days of injections. When buprenorphine treatment was terminated, G + S intake decreased even further. These lower rates of intake persisted for at least 5 days, and they returned to baseline by 2 weeks. Saline self-administration was decreased by buprenorphine in all saline extinction groups. Food intake was not altered by buprenorphine in the groups self-administering IV cocaine or saline; however, food intake was reduced in the G + S groups. Water intake increased during buprenorphine treatment in some of the cocaine groups but not in the G + S groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Determinants of increased drug self-administration due to food deprivation.

Changes in oral etonitazene self-administration were compared in four groups of rats that were maintained at 100, 95, 85, or 75% of their pre-experimental free-feeding body weights. Etonitazene (5 micrograms/ml) or water was available for 16 h according to a fixed-ratio (FR) 1 schedule. Each liquid delivery (0.1 ml) was contingent upon a lever-press response. During food deprivation etonitazene intake gradually increased to over two-fold as body weights decreased over 25 sessions; etonitazene intake was inversely proportional to body weight. The 75% weight group showed stereotypy, self-mutilation and large variability in daily etonitazene intake. In another experiment a range of deprivation conditions was studied in a group of six rats with etonitazene (5 micrograms/ml) or water available on an FR 8 schedule during 1-h sessions. When the rats were gradually food satiated, etonitazene-maintained behavior declined but remained higher than water-maintained behavior; however, when they were abruptly food satiated, etonitazene-maintained behavior decreased to low levels.

Autoshaping i.v. cocaine self-administration in rats: effects of nondrug alternative reinforcers on acquisition.

The purpose of this experiment was to examine the effects of a nondrug alternative reinforcer and feeding conditions on the acquisition of cocaine self-administration. Rats were autoshaped to press a lever that resulted in a 0.2 mg/kg i.v. cocaine infusion. Responses on the lever were monitored during six consecutive autoshaping sessions that occurred each day. A retractable lever was inserted into the operant chamber on a random time 60 s schedule 10 times per session for six sessions that began each hour. Each day the six autoshaping sessions were followed by a 6-h cocaine self-administration session. During self-administration the lever remained extended, and each response on the lever resulted in a cocaine infusion (0.2 mg/kg). The criterion for acquisition of cocaine-reinforced behavior was met when there were 5 consecutive days during which the mean number of infusions during the 6-h self-administration session was at least 100. This procedure was repeated daily until the criterion was met or 30 days elapsed. The rats were also trained to respond on lick-operated automatic drinking devices that delivered 0.05 ml water or a glucose and saccharin solution (G + S) contingent upon each lick response. Five groups of 12-14 rats were compared. The first four groups constituted a 2 x 2 factorial design whereby either G + S or water was available in the home cage for 3 weeks before autoshaping began and G + S or water was available in the operant chamber during autoshaping. These groups were limited to 20 g food per day and all had free access to water.(ABSTRACT TRUNCATED AT 250 WORDS)

Progressive ratio and behavioral economic evaluation of the reinforcing efficacy of orally delivered phencyclidine and ethanol in monkeys: effects of feeding conditions.

The effect of feeding conditions on the reinforcing efficacy of orally-delivered drugs was evaluated using a progressive-ratio (PR) paradigm and a behavioral economic analysis of demand. Seven monkeys self-administered phencyclidine (PCP) (0.06, 0.12, 0.25, 0.5, and 1.0 mg/ml) or ethanol (2, 4, 8, 16, and 32% wt/vol) and concurrent water from two drinking spouts under concurrent PR schedules. The ratios increased from 8 to 4096, and 40 liquid deliveries were available after completion of each ratio schedule. The entire range of drug concentrations was presented in nonsystematic order under two feeding conditions, food restriction and food satiation. Drug maintained responses, deliveries and break points were significantly greater than those maintained by water. Food restriction significantly increased the rate of PCP-maintained responses, deliveries and PR break points over the food satiation baseline. There was also a significant interaction between feeding condition and drug concentration. Although ethanol-maintained responses, liquid deliveries and break points consistently increased in five of seven monkeys during food restriction, only drug concentration produced significant differences in these measures. Using break point as a measure of reinforcing efficacy, food restriction increased the reinforcing efficacy of PCP and had a more pronounced effect at higher drug unit prices.

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.

Effects of food FR and food deprivation on disruptions in food-maintained performance of monkeys during phencyclidine withdrawal.

Six rhesus monkeys self-administered orally-delivered phencyclidine (PCP) and water under concurrent fixed-ratio (FR) 8 schedules. Liquids were available during three 6.5-h periods daily preceded by 1-h components when food was available under an FR 64 (lever press) schedule. After 10 days of stable behavior, water was substituted for PCP for 8 days. PCP was subsequently reinstated, and this PCP withdrawal sequence was repeated using different food FR values (64, 128, 256, 512 and 1024). Each time the food FR was changed behavior was allowed to stabilize for at least 10 days. Under all FR values food-maintained responding decreased markedly during PCP withdrawal, with a gradual recovery over the next 8 days. As the FR value increased from 64 to 1024 there was a parallel shift downward in food-maintained performance. When PCP was reinstated, food-reinforced responding generally returned to baseline rates during the first few days. In a second experiment monkeys were tested for PCP withdrawal effects under relatively food deprived or food satiated conditions under both an FR 512 and 1024 schedule of food delivery. The results showed that the decrease in food-maintained responding during withdrawal was inversely related to the total amount of food consumed during the control period. The results of these experiments indicate that manipulation of both the response requirements for food (FR) and the total amount of food available (food deprivation/satiation) alters the magnitude of response disruptions during PCP withdrawal.

A comparison of progressive ratio schedules versus behavioral economic measures: effect of an alternative reinforcer on the reinforcing efficacy of phencyclidine.

Alternative non-drug reinforcers have been demonstrated to decrease drug-reinforced behavior by both decreasing relative reinforcing efficacy and substituting for the drug reinforcer. The effect of saccharin on responding maintained by orally delivered phencyclidine (PCP) was examined in this study using concurrent progressive-ratio (PR) schedules of reinforcement and a behavioral economic analysis of demand. Seven adult male rhesus monkeys self-administered PCP (0.06, 0.12, 0.25, 0.50 and 1.0 mg/ml) and either concurrent water or saccharin (0.03% wt/vol) from two drinking spouts under concurrent independent PR schedules. During daily sessions the response requirements (lip contacts on automatic drinking spouts) increased across 15 levels, from 8 to 4096. Each successful ratio completion resulted in the availability of 40 liquid deliveries under an FR 1 schedule and a subsequent increment in the PR. Concentrations of PCP were presented in a non-systematic order and presentation of the concurrent liquid, saccharin or water, was counterbalanced across subjects. All behaviors maintained by PCP were significantly greater than those maintained by water. Replacement of water with saccharin served to significantly decrease PCP-maintained responding and break points (BP) across the range of PCP concentrations; however, saccharin did not significantly decrease deliveries of PCP. Saccharin maintained significantly greater responding, BPs and deliveries compared to either PCP or water, across all PCP concentrations. The use of BP as a measure of reinforcing efficacy suggests that saccharin decreased the relative reinforcing efficacy of PCP. Furthermore, behavioral economic analyses suggested that saccharin decreased maximal PCP-maintained responding (Pmax) in a similar fashion, suggesting that BP and Pmax may be analogous measures of reinforcing efficacy.

Concurrent progressive-ratio schedules to compare reinforcing effectiveness of different phencyclidine (PCP) concentrations in rhesus monkeys.

RATIONALE: Progressive ratio (PR) schedules have become well accepted for testing the reinforcing effectiveness of drugs. This study extends the methods to concurrent PR schedules with different concentrations of orally delivered phencyclidine (PCP). OBJECTIVE: The sensitivity of the procedure is tested by presenting different PCP concentrations with independently-operating PR schedules. METHOD: PCP self-administration was investigated in seven rhesus monkeys. Six different PCP concentrations (0.03-1.0 mg/ml) and water were randomly paired (21 pairings). Liquid delivery (24 ml) was contingent upon lip-contact responses on solenoid-operated drinking spouts; whereby, the response requirement or fixed-ratio (FR) increased (from 8 to 16, 32, 64, 128... to 4096) after each successful completion of a previous FR and subsequent liquid delivery. Monkeys self administered PCP during daily 3-h sessions, and each pair of concentrations was held constant until behavior had stabilized for at least 4 days. RESULTS: The higher of the two PCP concentrations always maintained greater responding, PR break point (BP), or the last ratio completed, and liquid deliveries than did the lower concentration. However, the monkeys did not exclusively respond on the drinking spout that yielded the higher drug concentration. When examined across all drug pairings, the percentage of total available deliveries of the higher concentration was significantly greater than those of the lower concentration. The monkeys maximized the amount (mg) consumed for the response output. Responding, BPs and liquid deliveries maintained by 0.12 and 0.25 mg/ml PCP were significantly greater than other PCP concentrations; however, drug intake (mg) increased directly with PCP concentration. CONCLUSION: These results indicate that concurrent PR schedules using oral drug self-administration and a concurrent choice paradigm reliably provide an estimation of relative reinforcing strength, and behavior maintained by these schedules is sensitive to small changes in PCP concentration.

Effect of dose on increased etonitazene self-administration by rats due to food deprivation.

Rats were trained to self-administer IV-delivered etonitazene while food satiated. A wide range of etonitazene doses (5-80 micrograms/kg) and saline were tested under food satiation and food deprivation conditions. Food deprivation produced a parallel increase in the dose-response function under FR 1 and FR 16 schedule conditions.

Sex differences in the acquisition of intravenously self-administered cocaine and heroin in rats.

RATIONALE: Despite numerous reports that male and female animals differ in behavioral responses to drugs, few studies have investigated sex differences in drug-reinforced behavior. OBJECTIVES: Acquisition of IV cocaine and heroin self-administration was compared in 20 female and 22 male Wistar rats. METHODS: An autoshaping procedure was used to train rats to press a lever that resulted in either a 0.2 mg/kg infusion of cocaine or a 0.015 mg/kg infusion of heroin under a fixed-ratio 1 (FR 1) schedule. Daily sessions consisted of six 1-h autoshaping components followed by a 6-h self-administration component. During each autoshaping component, a retractable lever briefly (15 s) extended into the test chamber on a random interval schedule with a mean of either 90 s (cocaine groups) or 480 s (heroin groups) and either ten (cocaine groups) or five (heroin groups) computer-automated infusions were delivered each hour. During each 6-h self-administration component, the lever remained extended and each response on the lever resulted in an infusion of either cocaine (0.2 mg/kg) or heroin (0.015 mg/kg). The criterion for acquisition of cocaine self-administration was a mean of at least 100 infusions and the criterion for heroin self-administration was a mean of at least 20 infusions during the self-administration component over five consecutive sessions. RESULTS: Female rats acquired both cocaine and heroin self-administration more rapidly than males. Acquisition of cocaine self-administration occurred in a greater percentage of female rats compared to males. Female rats self-administered more cocaine than males after acquisition criteria had been met. CONCLUSIONS: These findings indicate that female rats were more vulnerable than males to the acquisition of cocaine and heroin self-administration under the conditions of the present experiment.