Early environmental enrichment and impoverishment differentially affect addiction-related behavioral traits, cocaine-taking, and dopamine D(2/3) receptor signaling in a rat model of vulnerability to drug abuse

RATIONALE: Risk factors for drug addiction include genetics, environment, and behavioral traits such as impulsivity and novelty preference (NP), which have been related to deficits in striatal dopamine (DA) D(2/3)-receptors (D(2/3)R) and heightened amphetamine (AMPH)-induced DA release. However, the influence of the early rearing environment on these behavioral and neurochemical variables is not clear. OBJECTIVES: We investigated the influence of early rearing environment on striatal D(2/3)R availabilities and AMPH-induced DA release in relation to impulsivity, NP, and propensity to drug self-administration (SA) in “addiction-prone” Roman high- (RHA) and “addiction-resistant” Roman low-avoidance (RLA) rats. METHODS: Animals were reared post-weaning in either environmental enrichment (EE) or impoverishment (EI) and were assessed at adulthood for impulsivity, NP, and propensity to cocaine SA. EE and EI rats were also scanned using single-photon emission computed tomography to concurrently measure in vivo striatal D(2/3)R availability and AMPH-induced DA release. RESULTS: EE vs. EI was associated with heightened impulsivity and a lack of NP in both rat lines. Higher dorsal striatal D(2/3)R densities were found in RHA EE and higher AMPH-induced DA release in RLA EE. Both impulsivity and NP were negatively correlated to dorsal striatal D(2/3)R availabilities and positively correlated with AMPH-induced DA release in EI but not in EE. EE vs. EI was related to a faster rate of cocaine intake and elevated active timeout responses in RHAs. CONCLUSION: Our results suggest non-monotonic, environment-dependent, relationships between impulsivity, NP, and D(2/3)R-mediated signaling, and suggest that EI vs. EE may decrease the reinforcing effects of psychostimulants in predisposed individuals. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00213-021-05971-z.