Effect of drug-paired exteroceptive stimulus presentations on methamphetamine reinstatement in rats

Abstract

The purpose of the present study was to examine the impact of drug-paired cues on methamphetamine reinstatement. Three groups of rats were trained to self-administer 0.1 mg/kg/infusion methamphetamine. Each methamphetamine infusion was accompanied by a 6 s flashing light+tone stimulus (cues). After training, the groups were then given 12, daily extinction sessions either with or without response-contingent drug-paired cues and then tested for 1 mg/kg i.p. methamphetamine priming-induced reinstatement either with or without cues. Methamphetamine priming significantly reinstated drug-appropriate responding regardless of whether response-contingent cues were omitted during both extinction and testing, presented during both extinction and testing, or omitted during extinction but presented during reinstatement testing. The group in which cues were omitted during extinction and presented during reinstatement exhibited significantly greater reinstatement than did the other two groups. A separate group of rats was also tested demonstrating that response-contingent presentation of previously methamphetamine-paired cues alone, without methamphetamine priming, significantly reinstated drug-appropriate responding. These data show that methamphetamine priming produces a robust reinstatement effect which can be influenced by drug-paired cues.

Figure 1

Self-administration and extinction responding: Left panels show responses (+/− SEM) on the methamphetamine-appropriate lever for each of the four test groups. Right panels show inactive-lever responding for each of the four groups. Symbols above SA show group mean responses per 2 h session on the final day of methamphetamine self-administration. Connected points show mean responses per 2 h session on all twelve extinction days for each of the four test groups. * denote significant differences (p < 0.05) in extinction responding compared to the final day of self-administration (SA).

Figure 2

Reinstatement responding: The upper panel shows active-lever responses (+/− SEM) on the final day of extinction and the reinstatement test session for each of the four test groups. The bottom panel shows inactive-lever responses for the same period. * denote significant increases in (p < 0.05) in reinstatement responding for each group compared to their last final day of extinction. # denote significant differences (p<0.05) in the magnitude of reinstatement between the groups linked by brackets.