Acute and chronic cocaine behavioral effects in novel versus familiar environments: open-field familiarity differentiates cocaine locomotor stimulant effects from cocaine emotional behavioral effects.

Cocaine is a potent stimulant drug, but its stimulant effects can be substantially modulated by environmental novelty versus familiarity. In this report, we varied exposures to a novel environment as a way to assess the impact of environmental familiarity versus novelty upon the locomotor activation induced by acute and chronic cocaine treatments. In experiment 1, the effects of 1 (PE1) versus 0 (PE0) pre-exposures to the test environment were compared for their impact upon the locomotor stimulant, central zone entry and grooming effects induced by an acute cocaine (10 mg/kg) treatment. In experiment 2, the effects of 10 (PE10) versus 0 (PE0) pre-exposures upon the cocaine effects were compared. Experiment 3 assessed the effects of nine cocaine treatments (10.0 mg/kg) initiated in a novel environment (PE0) versus familiar environment (PE10). In all experiments, cocaine had a potent locomotor stimulant effect in a novel environment, which was attenuated by environmental familiarity such that in PE10 groups, cocaine did not reliably induce an acute locomotor stimulant effect. Environmental novelty/familiarity, however, did not reliably alter cocaine effects upon central zone penetration, grooming behavior, or the neurochemical effects induced by cocaine. In the chronic treatment regimen, the PE0 group exhibited a tolerance-like decrease in locomotor activation, but the PE10 group exhibited a sensitization-like increase in locomotor activation. Despite the marked directional changes in the locomotor stimulant effects of cocaine treatments, initiated in a novel (PE0) versus familiar (PE10) environment, the same asymptotic levels of locomotor activation were achieved. In contrast, the behavioral measures of central zone activity progressively increased with repeated treatments regardless of whether the environment was initially novel (PE0) or familiar (PE10). Thus, habituation factors can profoundly alter the locomotor stimulant effects of cocaine and can induce pseudo-tolerance phenomena. In contrast, central zone activity undergoes sensitization-like effects independent of habituation state and therefore appears to represent a more fundamental behavioral effect of cocaine. In that, central zone penetration in an open-field is linked to emotional processes; this finding is of substantial importance in understanding the effects of repeated cocaine usage.