Lever-pressing responses of 55 rats were reinforced with IV-delivered cocaine (0.2 mg/kg) or saline under conditions of continuous access for 15 24-h sessions. The rats also responded on tongue-operated drinking devices for deliveries of a 3% (w/v) glucose + 0.125% (w/v) saccharin (G+S) solution or water. The effects of removing these substances on behavior maintained by G+S, water, cocaine, or saline were compared in 11 groups. Terminating cocaine access produced a decrease in G+S drinking and an increase in food and water intake. In contrast, a group of rats that did not initially self-administer G+S showed increases in G+S drinking when cocaine was removed, and G+S-maintained responding persisted when cocaine was reinstated. Substitution of water for G+S produced a nearly two-fold increase in cocaine-reinforced behavior but no change in IV-delivered saline self-administration in a control group. A group that did not initially self-administer cocaine increased its infusion rate to over 400 infusions per day as soon as G+S was replaced with water. The effect of presenting cocaine to a group that responded for G+S alone was to decrease G+S intake, but there was only a transient decrease in water intake in the control group. Likewise, presentation of G+S to a group of rats self-administering cocaine resulted in a decrease in infusions, but saline infusions did not change in a control group. Generally, there was an increase in food and water intake during cocaine removal, but food and water intake did not vary systematically with the removal or presentation of G+S.(ABSTRACT TRUNCATED AT 250 WORDS)

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)

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.

1) The magnitude of the suppressant effects of baclofen on maintenance of cocaine self-administration depends upon the maintenance dose, 2) baclofen may be useful in preventing reinstatement of cocaine-seeking behavior, and 3) compared to maintenance, reinstatement of responding is more sensitive to the suppressant effects of baclofen.

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