Novelty-induced locomoter activity in Long-Evans rats pre- and post-chronic 'binge'-pattern cocaine treatment.

Incremental locomotor activity observed in behaviorally sensitized rats is associated with the activation of the mesocorticolimbic dopaminergic system and the hypothalamic-pituitary-adrenal (HPA) axis. To determine whether individual locomotor differences are altered in the behaviorally sensitized state, Long-Evans rats were placed in a novel environment and locomotor activity was recorded for 2 h. Animals, thereby, were evenly divided into two activity groups: lower- (LR) and higher- (HR) responders (LR, 367 +/- 38 cumulative beam breaks; HR, 797 +/- 43; P < 0.01). Subsequently, rats were randomly assigned to saline or chronic 'binge'-pattern (CBP) cocaine (15 mg/kg i.p., three injections/day for 14 days) treatment groups. One hour after the last injection, rats were sacrificed and trunk blood was collected for plasma corticosterone (CORT) determination. CORT levels were higher in cocaine versus saline treated animals (P < 0.01). CBP cocaine treated rats had higher locomotor activity compared to saline treated animals (P < 0.05). Moreover, rats less vulnerable to psychostimulant self-administration (LRs) appeared to have locomotor behavior resembling that of the more vulnerable phenotype (HRs) after CBP cocaine. These findings suggest that behavioral sensitization, as a result of CBP cocaine treatment, changes novelty-stress induced behavior which may reflect altered individual vulnerability to drugs of abuse.