Impulsivity predicts the escalation of cocaine self-administration in rats

Abstract

Impulsivity, as measured by the delay-discounting task, predicts the acquisition of cocaine self-administration and reinstatement of cocaine seeking in rats. The purpose of this study was to extend these results to the escalation phase of drug self-administration. Female rats were initially screened for high (HiI) or low (LoI) impulsivity for food reinforcement using a delay-discounting procedure. They were then implanted with i.v. catheters and trained to lever press for cocaine infusions (0.8 mg/kg). Once cocaine intake stabilized, rats were allowed to self-administer cocaine (0.4 mg/kg) under a fixed-ratio 1 (FR 1) schedule during three, 2 h short-access sessions. Subsequently, performance was briefly assessed under a progressive ratio (PR) schedule for 3 doses of cocaine (0.2, 0.8, and 3.2 mg/kg). Following PR testing, the cocaine dose was then changed to 0.4 mg/kg. Session length was then extended to 6 h for 21 days (extended access), and 0.4 mg/kg cocaine was available under a FR 1 schedule. After the 21-day extended access phase, responses and infusions under the short access FR and PR dose-response conditions were reassessed. The results indicated that HiI rats escalated cocaine-reinforced responding during the extended access condition, but LoI rats did not. HiI rats also earned significantly more infusions than LoI rats under the post-escalation short access FR condition. However, HiI and LoI rats did not differ under the pre- and post-extended access PR conditions. This study suggests that individual differences in impulsivity predict escalation of cocaine self-administration in female rats, which may have implications in the prediction of binge-like patterns of cocaine intake in women.

Fig. 1

Mean (± SEM) cocaine infusions (0.4 mg/kg) are presented for each day of the extended access phase (6 hr) and for the last day of the short-access (ShA) condition (2 hr) before extended access (left unconnected points) and the first day of ShA after extended access (right, unconnected points). The inset represents mean cocaine infusions earned during the first 2 hr of extended access. Horizontal lines indicate the 3-day intervals during which there were significant group differences in responses or drug deliveries (ps < 0.05). During interval 1 (days 1-3) LoI rats earned more cocaine infusions than HiI rats (ps < 0.05). During interval 7 (days 19-21) the HiI group earned more infusions than the LoI group (ps < 0.05). HiI (vs LoI) rats also earned more infusions during interval 6 (days 15-18). * = p < 0.05 block 1 < blocks 3-7 in the HiI group. † = p < 0.05 ShA before vs. after extended access in the HiI group and HiI > LoI in ShA infusions after extended access (p < 0.05).

Fig. 2

Mean (± SEM) number of cocaine infusions earned by HiI and LoI rats under a PR schedule before (left panel) and after (right panel) extended access.