Reacquisition of heroin and cocaine place preference involves a memory consolidation process sensitive to systemic and intra-ventral tegmental area naloxone

Abstract

To investigate the effect of naloxone on a putative memory consolidation process underlying reacquisition of heroin and cocaine conditioned place preference, four studies were conducted in male Sprague-Dawley rats using a common procedure involving: place conditioning (0.3 or 1mg/kg heroin or 20mg/kg cocaine; x4 sessions), extinction (vehiclex4 sessions), and reconditioning (0 or 1mg/kg heroin or 20mg/kg cocaine; x1 session). Systemic naloxone injections (0, 1 and 3mg/kg) or bilateral intra-ventral tegmental area (VTA) naloxone methiodide infusions (2 nmol in 0.5 microl x side) were administered at different times following reconditioning. Post-reconditioning administration of naloxone dose-dependently blocked, attenuated and had no effect on reacquisition of heroin CPP when administered immediately, 1h and 6h after reconditioning, respectively. The highest dose of naloxone also blocked reacquisition of cocaine CPP, and did not produce a conditioned place aversion in heroin-naïve and heroin pre-treated animals. Post-reconditioning infusions in the VTA, but not in adjacent structures, blocked reacquisition of heroin CPP when administered immediately, but not 6h, after reconditioning. These data suggest that reacquisition of drug-cues associations involves a memory consolidation process sensitive to manipulations of the endogenous opioid system, and indicate that opioid receptors in the VTA may be critically involved in the re-emergence of drug seeking behavior.