Modulation of memory consolidation by heroin and heroin conditioned stimuli: roles of expectation and dopamine D1 receptor?

Abstract

Abstract It has been theorized that drugs of abuse have enhancing effects on memory consolidation, but recent evidence suggests that this cognitive effect may be mediated by mode of drug administration (i.e., passive vs active). Hence, two studies were designed to test the hypothesis that modulation of memory consolidation by heroin, and by a heroin conditioned stimulus (CS), may be mediated by a dopamine D1 receptor dependent mechanism of prediction error. Using male Sprague-Dawley rats and the object location memory task, Study 1 employed the D1 antagonist SCH23390 (0, 0.05, 0.10 mg/kg, subcutaneous, SC) to modulate enhancement of memory consolidation induced by post-training passive injections of heroin (1 mg/kg, SC) as well as by exposure to the environment paired with heroin injections (6 pairings, 1 h each, 1 mg/kg). Study 2 investigated the same hypothesis but in animals that could learn to predict heroin because the drug was self-administered (0.05 mg/kg/infusion, intravenous), and further explored whether SCH23390 (0 and 0.1 mg/kg) could prevent memory modulation induced by a change in schedule of self-administration (from fixed to variable ratio). It was found that while repeated passive injections of heroin retained their modulatory effect on memory, when self-administered, heroin enhanced consolidation of object location only at the beginning of self-administration and after a change in schedule. Importantly, SCH23390 blocked memory modulation by heroin when passively administered and when the drug was self-administered on a novel schedule. SCH23390 also blocked conditioned memory modulation induced by post-training exposure to the heroin-paired CS. Taken together, these results suggest that modulation of memory consolidation by unconditioned and conditioned opiate reinforcers may involve a DA D1-dependent mechanism that could be encoding the anticipation of drug effects.