Interactions between 18-methoxycoronasidine (18-MC) and cocaine: dissociation of behavioural and neurochemical sensitization

The phenomenon of sensitization has been implicated in various aspects of d rug addiction. As such, the present study determined the effects of a poten tial anti-addictive agent, 18-methoxycoronaridine (18-MG; 40 mg/kg, IF, 19 h earlier), on the expression of sensitization following the repeated admin istration of cocaine (COC; five once daily injections of 15 mg/kg, IF) or s aline. The effects of Is-MG on COC metabolism were also assessed. Compared to vehicle controls, Is-MG significantly enhanced the expression of COG-ind uced locomotion (0, 10, 20 and 40 mg/kg, IF) in chronic COC treated rats on ly. In both acute and chronic COC rats, 18-MG potentiated the stereotypy in duced by higher COC doses (20 and 40 mg/kg, IF). In contrast, 18-MG abolish ed the sensitized dopamine (DA) response in the nucleus accumbens (NAC) to COG (20 mg/kg), without altering the DA response of acute COC rats. None of the interactions between 18-MG and COC appear to be related to alterations in COC metabolism as no effect of Is-MG pretreatment was observed on extra cellular levels of COC or two of its metabolites, benzoylecogonine and norc ocaine. From the present findings, it is concluded that the enhancement of COG-induced behaviour produced by 18-MC pretreatment is independent of effe cts on either COC pharmacokinetics or COG-induced alterations in DA transmi ssion. However, given that 18-MG decreases the self-administration of COC i n laboratory animals, it is proposed that the anti-addictive efficacy of 18 -MG might be related to an ability to selectively block the expression of s ensitized extracellular levels of DA in the NAC in rats with previous COC e xperience. (C) 2000 Elsevier Science B.V. All rights reserved.