Enhancing effect of heroin on social recognition learning in male Sprague–Dawley rats: modulation by heroin pre-exposure

Abstract

There is evidence that pre-exposure to drugs of abuse can induce sensitization to several of their effects. Four experiments were conducted to investigate the effect of heroin pre-exposure on modulation of memory consolidation as indexed by heroin's action on rate of learning. Male Sprague-Dawley rats were tested on a social recognition learning task which assesses changes in investigation during repeated exposure to the same rat (habituation training: four sessions) and during exposure to a novel rat (dishabituation test). In the first experiment, rats received 0, 0.3, or 1 mg/kg heroin s.c. immediately following each training session, or 1 mg/kg heroin 2 h post-training. In experiments 2 and 3, rats received 1 mg/kg heroin post-training after a 7-day drug-free period from heroin pre-exposure achieved through conditioned place preference (1 mg/kg s.c., 1 injection/day x 4 days) or intravenous self-administration (0.05 mg/kg/infusion i.v., 3 h/day x 9 days) training. In experiment 4, rats received 0, 0.03, 0.3, or 3 mg/kg heroin post-training after a 7-day drug-free period from a regimen of heroin administration (i.e., 1 mg/kg heroin/day s.c. x 7 days) that induced locomotor sensitization. Post-training administration of heroin enhanced social recognition learning in a dose- and time-dependent manner. Importantly, no regimen of heroin pre-exposure significantly altered this effect of heroin. These results do not support the hypothesis that heroin pre-exposure leads to sensitization to its effect on memory consolidation of non-drug-related learning. However, this requires further testing using alternative heroin pre-exposure regimens, a wider range of post-training heroin doses, as well as other types of learning tasks.