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 whether differences in control rates of behavior are taken into account.

Individual Differences and Social Influences on the Neurobehavioral Pharmacology of Abused Drugs

“…In contrast to acute treatment, repeated stimulant treatment, including nicotine, is increased in IC rats relative to EC rats (Bardo et al, 1995;Funk et al, 2005;Solinas et al, 2009;Wooters et al, 2011). One caveat in these findings is that IC rats have higher baseline activity than EC rats before any drug treatment, which can complicate interpretation of the findings (Smith et al, 2009). That is, similar to inherent differences in activity between HR and LR rats, the conclusions drawn for IC and EC rats may differ depending on whether drug-induced hyperactivity is expressed as an absolute value or as a percent change relative to the different baselines.…”

“…This difference is greater at low unit doses than at high unit doses delivered on either FR or PR schedules. Although baseline differences in lever pressing between IC and EC rats need to be considered as described previously (Smith et al, 2009), evidence indicates that differential housing alters sensitivity to the reinforcing effects of abused drugs independent of baseline rates of lever pressing. For example, although IC rats have higher baseline (nonreinforced) rates of lever pressing, they acquire food-reinforced lever pressing at a slower rate than do EC rats (Bardo et al, 2001).…”

Genotype-dependent effects of adolescent nicotine exposure on dopamine functional dynamics in the nucleus accumbens shell in male and female mice: a potential mechanism underlying the gateway effect of nicotine

“…Among these are sex (Bobzean et al 2010;Vansickel et al 2010), environmental enrichment (Chauvet et al 2009;Smith et al 2009;Thiel et al 2010), group housing (van der Veen et al 2007), maternal environment (van der Veen et al 2008), social status (Morgan et al 2002), and socioeconomic status in humans (Humensky 2010;Lemstra et al 2008). In some cases, these factors, like adolescent nicotine exposure in the current study, have been shown to interact with genetic background (van der Veen et al 2008(van der Veen et al , 2007.…”

Environmental enrichment reduces methamphetamine cue-induced reinstatement but does not alter methamphetamine reward or VMAT2 function

“…EC rats also fail to reinstate extinguished responding following a dose of amphetamine (0.25 mg/kg) that reinstates responding in IC rats [8]; a higher dose of amphetamine (1 mg/kg) reinstates responding in both groups. While baseline (no drug) differences in rates of responding between EC and IC rats exist [9], these results overall indicate that enrichment may raise the primary reinforcement and reinstatement thresholds for engendering stimulant self-administration and stimulant seeking.…”