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 antagonist MK-801 or by prior ibotenic acid lesions of the medial prefrontal cortex (PFC). The present study examined the effect of these treatments on the expression of cocaine sensitization. Rats were treated with 15 mg/kg cocaine 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 expression. Rather, it augmented the response of sensitized rats to cocaine challenge and produced a non-significant trend towards augmentation of the acute response to cocaine in saline-pretreated rats. For PFC lesion experiments, 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 degree of sensitization. Thus, neither NMDA receptor transmission nor PFC projections appear necessary for the expression of cocaine sensitization.
Li
Y
Y
Department of Neuroscience, FUHS/The Chicago Medical School, North Chicago, IL 60064-3095, USA.
Wolf
M E
ME
White
F J
FJ
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000517:prevention & control*; D016291:Dizocilpine Maleate / Q000008:administration & dosage*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D007051:Ibotenic Acid / Q000008:administration & dosage*; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007051:Ibotenic Acid; D016291:Dizocilpine Maleate; D003042:Cocaine