Generalization of effects of environmental enrichment on seeking for different classes of drugs of abuse.

BACKGROUND: Addiction is a chronic disease characterized by persistent vulnerability to relapse during abstinence. In animal models of addiction, accumulating evidence suggests that exposure to environmental enrichment (EE) during periods of abstinence can have curative effects on addiction and reduce the risks of relapse. However, until present most studies have mainly focused on cocaine. In this study, we investigated whether EE could have beneficial effects on cue-induced seeking for several psychoactive drugs belonging to different pharmacological classes such as methamphetamine (METH), heroin (HER) and nicotine (NIC). METHODS: After self-administration training of METH, HER and NIC, rats were housed in enriched (EE) or standard environments (SE) for 21-28 days of forced abstinence and then drug-seeking behavior was assessed in the absence of the drug. RESULTS: We found that, compared to SE housing, exposure to EE reduced drug seeking behavior for all drugs tested. CONCLUSIONS: These findings suggest that the anti-craving effects of EE are general for a wide variety of drugs and support the hypothesis that environmental stimulation may be a general intervention for attenuating relapse in humans.

Behavioral flexibility predicts increased ability to resist excessive methamphetamine self-administration.

Drug addiction is often associated with cognitive deficits and behavioral inflexibility that may contribute to the development and maintenance of addictive behaviors by reducing addicts' ability to control their behavior toward the drug. In this study, we investigated the relationships between pre-drug levels of behavioral flexibility and the risk to develop uncontrolled methamphetamine (METH) self-administration. First, we measured individual performance in an inter-dimensional set-shifting procedure in which animals have to switch between an external visual rule and an internal side rule in order to obtain food pellets. Then we allowed rats to self-administer METH for twenty long 14-hour sessions, and we investigated the relationships between behavioral flexibility and measures of control over drug intake. Rats rapidly acquired to self-administer high levels of METH which resulted in moderate weight loss. After several sessions of self-administration, whereas some rats progressively increased their METH intake, other rats showed very long voluntary pauses between drug injections and showed no escalation in METH self-administration. Interestingly, we found that behavioral flexibility is correlated with METH self-administration and that more flexible rats take less METH and do not escalate drug taking. These results suggest that traits of behavioral flexibility may protect against the development of excessive and dysregulated drug taking. Conversely, the inability to adapt behavioral responses as a function of the environmental contingencies may contribute to the risks to develop addiction to METH.