Individual differences in behavioral responses to novelty and amphetamine self-administration in male and female rats

Previous work has shown that individual differences in locomotor activity in an inescapable novel environment can predict acquisition of amphetamine self-administration. The current study examined whether individual differences in approach to novelty in a free choice test could also predict amphetamine self-administration. Further, the current study examined whether individual differences in either free choice or inescapable novelty tests could predict responding for a nondrug reinforcer (sucrose) in the presence and absence of amphetamine. Male and female rats were first tested for their response to free choice novelty (playground maze and novelty-induced place preference tests) and inescapable novelty. They were then tested for acquisition of sucrose-reinforced responding, amphetamine-induced changes in maintenance of sucrose-reinforced responding, and amphetamine self-administration. Based on the inescapable novelty test, acquisition of sucrose-reinforced responding was more rapid in male high responders (HR) compared to low responders (LR). This effect in males did not generalize to females. None of the novelty tests predicted the ability of amphetamine to decrease sucrose-maintained responding. However, using the inescapable novelty test, both male and female HRs self-administered more amphetamine than LRs within the dose range tested (0.03-0.16mg/ kg/infusion). Neither the playground maze nor the novelty-induced place preference test predicted amphetamine self-administration. These results indicate that responses to free choice novelty and inescapable novelty predict different components of amphetamine-induced behavior

Lobeline attenuates d-methamphetamine self-administration in rats

ABSTRACT ␣-Lobeline inhibits d-amphetamine-evoked dopamine release from striatal slices in vitro, appearing to reduce the cytosolic pool of dopamine available for reverse transport by the dopamine transporter. Based on this neurochemical mechanism of action, the present study determined if lobeline decreases d-methamphetamine self-administration. Rats were surgically implanted with jugular catheters and were trained to lever press on a fixed ratio 5 schedule for intravenous d-methamphetamine (0.05 mg/kg/infusion). To assess the specificity of the effect of lobeline, another group of rats was trained to lever press on a fixed ratio 5 schedule for sucrose reinforcement. Pretreatment of rats with lobeline (0.3-3.0 mg/kg, 15 min prior to the session) decreased responding for both d-methamphetamine and sucrose reinforcement. Following repeated lobeline (3.0 mg/kg) administration, tolerance developed to the decrease in responding for sucrose; however, the lobeline-induced decrease in responding for d-methamphetamine persisted. Furthermore, the lobeline-induced decrease in responding for d-methamphetamine was not surmounted by increasing the unit dose of d-methamphetamine. These results suggest that lobeline produces a nonspecific rate suppressant effect following acute administration, to which tolerance develops following repeated administration. Importantly, the results also suggest that repeated administration of lobeline specifically decreases responding for d-methamphetamine in a noncompetitive manner. Thus, lobeline may be an effective, novel pharmacotherapy for d-methamphetamine abuse

Individual differences in response to novelty, amphetamine-induced activity and drug discrimination in rats

Rats mere pre-tested in several individual difference screens - novelty-induced activity, novelty-induced place preference, novel-object interaction, and amphetamine-induced activity. Rats that were more sensitive to the locomotor effects of amphetamine were more active in an inescapable novel environment and displayed a greater preference for a novel environment. All animals were then trained to discriminate amphetamine (1 mg/kg) from saline in a two-bar discrimination procedure using food-maintained responding. After acquisition of the discrimination (mean =37 trials), two amphetamine generalization tests (0.0625,0.125,0.25,0.5, 1.0 and 2.0 mg/kg) were conducted. In the second generalization test, rats that were more sensitive to the activating effect of amphetamine were also more sensitive to the discriminative stimulus effects of amphetamine (i.e. lower median effective dose). Moreover, high responders in the novelty-induced activity and novelty-induced place preference screens were more sensitive than low responders to the bar-press suppressant effects of amphetamine in the first generalization test. The relationships are discussed in terms of identifying processes common to the screens (e.g. stress and reward)