Cocaine-induced reinstatement of a conditioned place preference in developing rats: involvement of the d2 receptor.

Kimberly Badanich,Cheryl Kirstein

doi:10.3390/brainsci2040573

Abstract

Reinstatement of conditioned place preferences have been used to investigate physiological mechanisms mediating drug-seeking behavior in adolescent and adult rodents; however, it is still unclear how psychostimulant exposure during adolescence affects neuron communication and whether these changes would elicit enhanced drug-seeking behavior later in adulthood. The present study determined whether the effects of intra-ventral tegmental area (VTA) or intra-nucleus accumbens septi (NAcc) dopamine (DA) D2 receptor antagonist infusions would block (or potentiate) cocaine-induced reinstatement of conditioned place preferences. Adolescent rats (postnatal day (PND 28–39)) were trained to express a cocaine place preference. The involvement of D2 receptors on cocaine-induced reinstatement was determined by intra-VTA or intra-NAcc infusion of the DA D2 receptor antagonist sulpiride (100 μM) during a cocaine-primed reinstatement test (10 mg/kg cocaine, i.p.). Infusion of sulpiride into the VTA but not the NAcc blocked reinstatement of conditioned place preference. These data suggest intrinsic compensatory mechanisms in the mesolimbic DA pathway mediate responsivity to cocaine-induced reinstatement of a conditioned place preference during development.

Highlights

Place conditioning and cocaine-induced reinstatement paradigms have provided a measure of drug reward by assessing an animal’s ability to associate drug-induced effects with environmental cues.Cocaine place preferences were effectively established for adolescent and adult rodents at standard cocaine doses [1,2,3,4]
The present study examined the function of ventral tegmental area (VTA) and
All rats were exposed to conditioned place preference training during adolescence (PND 30–38)

Summary

Introduction

Cocaine place preferences were effectively established for adolescent and adult rodents at standard cocaine doses [1,2,3,4]. Balda and colleagues [4] were the first to demonstrate adolescent mice were able to express cocaine-induced reinstatement of cocaine place conditioning while a more recent report suggested age effects for cocaine-induced reinstatement of a conditioned place preference were dose dependent [5]. When lower doses were tested, early adolescents demonstrated place preferences for lower doses of cocaine than late adolescent and adult rats indicating that early adolescent rats were more responsive to the rewarding properties of a low dose of cocaine than older rats [3]. In vivo microdialysis has shown psychostimulants increased DA in the nucleus accumbens septi (NAcc) of preadolescent [17] and adolescent rodents [3,16,18,19]

Methods

Results

Discussion

Conclusion