Effects of extended cocaine conditioning in the reinstatement of place preference.

Rats allowed extended access to cocaine self-administration develop a number of symptoms of addiction, such as greater susceptibility to drug-induced relapse. Using the conditioned place preference (CPP), the number of conditioning training sessions was increased in order to augment exposure to contextual cues associated with the effects of a drug. Mice were conditioned with a steady dose of 6 or 25 mg/kg of cocaine for 4, 8, 12, 16, 20 or 40 days. Weekly sessions of extinction followed the establishment of preference, after which a priming dose of cocaine was administered to reinstate the extinguished preference. The magnitude of the place preference effect was equal in all groups, independently of the number of conditioning sessions. The persistence of the place preference was not related with the number of sessions. Higher responsiveness to reinstatement of the extinguished preference occurred only with an intermediate number of conditioning sessions. In this way, the relation between the number of training sessions and vulnerability to relapse appeared to follow an inverted U-shaped function. Our results suggest that increasing the number of conditioning sessions from 12 to up to 16, without increasing the amount of drug administered, can be of great use in the study of vulnerability to relapse.