Acquisition of IV amphetamine and cocaine self-administration in rats as a function of dose

Abstract

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.

Heroin self-administration and reinstatement of heroin-seeking in adolescent vs. adult male rats

“…We had hypothesized that adolescent rats would be more sensitive than adults to the acute reinforcing effects of heroin and predicted that this would be reflected as lower rates of drug intake on a FR schedule of reinforcement with the doses we tested on the descending limb of a dose-effect function (Arnold and Roberts 1997;Carroll and Lac 1997;Koob et al 1984). In other words, higher potency of heroin in adolescents would produce a leftward shift in the inverted U-shaped function.…”

Behavioral characteristics and neurobiological substrates shared by Pavlovian sign-tracking and drug abuse

“…For example, Carroll and her associates have reported that pairings of the insertion of a lever CS with intravenous administration of drug reward US induced the automatic "shaping" of lever-pressing for drug self-administration in rats. Procedures of this sort have been employed to induce reliable leverpressing for the self-administration of the cocaine US (Carroll and Lac, 1993, 1998Specker et al, 1994;Gahtan et al, 1996;Lynch and Carroll, 1999;Lynch et al, 2001;Campbell and Carroll, 2001;Campbell et al, 2002;Carroll et al, 2002;Roth et al, 2002; see also Panlilio et al, 1996;Weiss et al, 2003 c.f., Di Ciano andKearns and Weiss, 2004), orthe self-administration of the amphetamine US (Carroll and Lac, 1997) or the self-administration of the heroin US (Lynch and Carroll, 1999;Carroll et al, 2002;Roth et al, 2002). In all of these studies, rats developed increasingly frequent lever-pressing as a function of experience with repeated pairings of lever CS with rewarding drug US.…”

Developmental lead exposure alters methamphetamine self-administration in the male rat: Acquisition and reinstatement

“…This value is half of what has been set previously in studies that used twice the duration of testing time [i.e., 6-hr autoshaping and 6-hr self-administration] (e.g., Carroll and Lac, 1997). The methamphetamine dose (0.02 mg/ kg/inf) was chosen based on data from previous studies that show this dose is marginally reinforcing, and does not produce satiation or motoric impairments (Roth and Carroll, 2004).…”

“…It has been argued that the rate of acquisition of drug selfadministration may serve as a predictor of later drug-taking behavior, possibly influencing the transition from drug use to addiction (refer to Rocha et al, 2005). Accordingly, in Experiment 1 an acquisition paradigm developed by Carroll and associates (Campbell and Carroll, 2001;Carroll and Lac, 1997) was employed to train lead-exposed and control animals to press a lever for a methamphetamine-reinforcement in a consistent manner, with minimal intrusions. In this preparation, Pavlovian conditioning is first used to shape behavior, then operant conditioning is tested in order to measure rate of methamphetamine acquisition in the animals.…”