Role of dopamine D1 receptor in the modulation of memory consolidation by passive and self-administered heroin and associated conditioned stimuli

Abstract

It has been proposed that opiates modulate memory consolidation, but recent work has indicated that this effect may be mediated by how the drug is experienced (i.e., passive injections vs. self-administration). Because the dopamine (DA) D1 receptor is involved in processing of learning signals and attribution of salience to events experienced by an organism, two studies in male Sprague-Dawley rats tested the effect of blocking this receptor on modulation of memory consolidation by passive and self-administered heroin, in addition to conditioned memory modulation by heroin-paired cues. Using the object location memory task, Study 1 employed SCH23390 (0, 0.05, 0.10 mg/kg, SC) to modulate enhancement of memory consolidation induced by post-training 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 was conducted in rats that could self-administer heroin (0.05 mg/kg/infusion, IV) and tested whether SCH23390 (0 and 0.1 mg/kg, SC) 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 enhancing effect on memory, when self-administered, heroin enhanced consolidation of object location memory 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 heroin-paired cues. Taken together, these results suggest that modulation of memory consolidation by unconditioned and conditioned opiate reinforcers involve a D1-dependent mechanism of salience attribution linked to the anticipation of drug effects.

Figure 1

Panel (A): experimental design employed in Study 1 showing the relationship between the tests of object location memory and sessions of conditioning/passive heroin injection and exposure to the heroin CS in the absence of heroin. Panel (B): experimental design employed in Study 2 showing the relationship between the tests of object location memory and sessions of heroin self-administration.

Figure 2

Panel (A): mean (SEM) DRs from sample and choice phases of rats (n = 52) administered 1 mg/kg heroin post-sample to test memory modulation by the first conditioning session. Panel (B): mean (SEM) DRs from sample and choice phases of rats that received injections of 1 mg/kg heroin but no SCH (No SCH group; n = 16), or immediate post-sample injections of either 0, 0.05 or 0.10 mg/kg SCH23390 (n = 12 per group) followed by 1 mg/kg injections of heroin. Panel (C): mean (SEM) DRs from sample and choice phases of rats that received either 0 or 0.10 mg/kg SCH23390 (n = 8 per condition) immediately post-sample followed by exposure to the heroin context CS. The * indicates a significant difference between phases.

Figure 3

Panel (A): mean (SEM) active and inactive lever presses, as well as infusions, during the 11 sessions of heroin self-administration on FR1 (n = 37). Panel (B): mean (SEM) active and inactive lever presses, as well as infusions, for No SCH (n = 18), 0 SCH (n = 10), and 0.10 SCH (n = 9) groups during the session of self-administration on a VR20 schedule. The * indicates a significant difference between levers. The # indicates a significant difference between groups.

Figure 4

Panels (A,B): mean (SEM) DRs from sample and choice phases of rats (n = 37) on the test of memory modulation by self-administration sessions 1 and 6, respectively. Panel (C): mean (SEM) DRs from sample and choice phases of FR1 only (n = 16), No SCH (n = 18), 0 SCH (n = 10), and 0.10 SCH (n = 9) groups on the test of memory modulation by the 12th session of heroin self-administration. The * indicates a significant difference between phases.