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Title: NMDA receptor inhibition prevents tolerance to cocaine. Author: De Montis MG, Devoto P, Meloni D, Gambarana C, Giorgi G, Tagliamonte A. Journal: Pharmacol Biochem Behav; 1992 May; 42(1):179-82. PubMed ID: 1356273. Abstract: Male rats were treated with cocaine by utilizing two different experimental paradigms. One group of animals received a low dose (10 mg/kg, IP) of cocaine for 7 days. A second group received 40 mg/kg IP of cocaine for 3 days. In both experimental groups, half the animals were concomitantly treated with 0.25 mg/kg IP (+)-5methyl-10,11-dihydro-5H-dibenzo-[a,d]-cyclohepten-5,10- imine maleate (MK-801), a noncompetitive NMDA receptor antagonist. Rats treated with the low dose of cocaine after 7 days developed tolerance to the stimulation of locomotor activity induced by cocaine and by the dopamine D2 agonist quinpirole. Rats treated with 40 mg/kg of cocaine showed a marked behavioral sensitization. Both these effects, tolerance and sensitization, were prevented by coadministration of MK-801, thus suggesting these two phenomena are different aspects of a common neuronal response in which NMDA transmission plays a crucial role.[Abstract] [Full Text] [Related] [New Search]