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Updated: Oct 15, 2026

Assessment of Cocaine-induced Behavioral Sensitization and Conditioned Place Preference in Mice
Published on: February 18, 2016
Interactions between 18-methoxycoronaridine (18-MC) and cocaine: dissociation of behavioural and neurochemical
K K Szumlinski1, C A McCafferty, I M Maisonneuve
1Center for Neuropharmacology and Neuroscience (MC-136), Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USA. szumlik@mail.amc.edu
Abstract:
The phenomenon of sensitization has been implicated in various aspects of drug addiction. As such, the present study determined the effects of a potential anti-addictive agent, 18-methoxycoronaridine (18-MC; 40 mg/kg, IP, 19 h earlier), on the expression of sensitization following the repeated administration of cocaine (COC; five once daily injections of 15 mg/kg, IP) or saline. The effects of 18-MC on COC metabolism were also assessed. Compared to vehicle controls, 18-MC significantly enhanced the expression of COC-induced locomotion (0, 10, 20 and 40 mg/kg, IP) in chronic COC treated rats only. In both acute and chronic COC rats, 18-MC potentiated the stereotypy induced by higher COC doses (20 and 40 mg/kg, IP). In contrast, 18-MC abolished the sensitized dopamine (DA) response in the nucleus accumbens (NAC) to COC (20 mg/kg), without altering the DA response of acute COC rats. None of the interactions between 18-MC and COC appear to be related to alterations in COC metabolism as no effect of 18-MC pretreatment was observed on extracellular levels of COC or two of its metabolites, benzoylecogonine and norcocaine. From the present findings, it is concluded that the enhancement of COC-induced behaviour produced by 18-MC pretreatment is independent of effects on either COC pharmacokinetics or COC-induced alterations in DA transmission. However, given that 18-MC decreases the self-administration of COC in laboratory animals, it is proposed that the anti-addictive efficacy of 18-MC might be related to an ability to selectively block the expression of sensitized extracellular levels of DA in the NAC in rats with previous COC experience.
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