Effects of environmental enrichment on sensitivity to cocaine in female rats: importance of control rates of behavior

Abstract

Environmental enrichment produces functional changes in mesolimbic dopamine transmission and alters sensitivity to psychomotor stimulants. These manipulations also alter the control rate of many behaviors that are sensitive to stimulant administration, which can make comparison of drug effects between isolated and enriched subjects difficult. The purpose of this study was to examine the effects of environmental enrichment on control rates of behavior and on sensitivity to cocaine in tests of locomotor activity, drug self-administration, conditioned place preference, and toxicity. In the locomotor activity test, isolated rats exhibited greater activity after the administration of cocaine, but also had higher control rates of activity. When locomotor activity was expressed as a percentage of saline control values, enriched rats exhibited a greater increase relative to their own control than isolated rats. In the drug self-administration procedure, isolated rats had higher breakpoints on a progressive-ratio schedule of reinforcement when responding was maintained by cocaine; however, isolated rats also had higher breakpoints in saline substitution tests and higher rates of inactive lever responding. When the self-administration data were expressed as a percentage of these control values, enriched rats exhibited a greater increase in responding relative to their own control rates than isolated rats. No differences were observed between isolated and enriched rats under control conditions in the place preference and toxicity studies. In both of these procedures, enriched rats were more sensitive than isolated rats to all the doses of cocaine tested. These data emphasize the importance of considering control rates of behavior in studies examining environmental enrichment and drug sensitivity, and suggest that environmental enrichment increases sensitivity to cocaine across a range of dependent measures when differences in control rates of behavior are taken into account.

Fig. 1

Locomotor activity in isolated and enriched rats (mean ±SEM). Top panel: locomotor activity expressed as distance traveled (cm) during three consecutive components of the saline control session. Middle panel: locomotor activity expressed as distance traveled (cm) after cumulative doses of cocaine. Bottom panel: locomotor activity expressed as a percentage of saline control values after cumulative doses of cocaine.

Fig. 2

Drug self-administration in isolated and enriched rats (mean ±SEM). Upper panel: breakpoints expressed as number of infusions (left axis) and number of active lever presses (right axis) on a progressive-ratio schedule of reinforcement. Lower panel: number of inactive lever presses under each dose condition.

Fig. 3

Cocaine self-administration in isolated and enriched rats (mean ±SEM). Upper panel: breakpoints expressed as a percentage of saline control values when responding was maintained by various doses of cocaine. Lower panel: active lever responding expressed as a percentage of inactive lever presses when responding was maintained by various doses of cocaine.

Fig. 4

Difference scores of isolated and enriched rats in the conditioned place preference procedure (mean ±SEM). All data reflect change in time (s) spent in the drug-paired compartment after conditioning.

Fig. 5

Cocaine-induced toxicity in isolated and enriched rats (mean ±SEM). All data reflect convulsive activity based on a 5-point scale.