The expression of cocaine sensitization is not prevented by MK-801 or ibotenic acid lesions of the medial prefrontal cortex

Previous work has established that the development of cocaine sensitization is prevented by co-administration of the non-competitive NMDA receptor ant agonist MK-801 or by prior ibotenic acid lesions of the medial prefrontal c ortex (PFC). The present study examined the effect of these treatments on t he expression of cocaine sensitization. Rats were treated with 15 mg/kg coc aine for 5 days and then challenged with cocaine 3 days later to establish the presence of sensitization. The next day, rats received 0.1 mg/kg MK-801 30 min before cocaine challenge. This dose of MK-801, which is sufficient to prevent the development of cocaine sensitization, did not prevent its ex pression. Rather, it augmented the response of sensitized rats to cocaine c hallenge and produced a non-significant trend towards augmentation of the a cute response to cocaine in saline-pretreated rats. For PFC lesion experime nts, rats were sensitized to cocaine and then received either ibotenic acid or sham lesions of the PFC. One week later, all rats were challenged with cocaine. Sham lesioned and ibotenic acid lesioned rats exhibited the same d egree of sensitization. Thus, neither NMDA receptor transmission nor PFC pr ojections appear necessary for the expression of cocaine sensitization. (C) 1999 Elsevier Science B.V. All rights reserved.