The potential anti-addictive agent, 18-methoxycoronaridine, blocks the sensitized locomotor and dopamine responses produced by repeated morphine treatment

18-Methoxycoronaridine (18-MC), a novel synthetic iboga congener, attenuate s the reinforcing efficacy of morphine, disrupts some signs of morphine wit hdrawal in physically dependent rats and attenuates the dopamine response i n the nucleus accumbens to acute morphine. The present study further invest igated the interactions between 18-MG and morphine by examining the effects of 18-MG (40 mg/kg, i.p., 19 h earlier) on the expression of dopamine sens itization in the nucleus accumbens in response to morphine (20 mg/kg, i.p.) and on the dose-effect curves for morphine-induced locomotion (0-30 mg/kg, i.p.) in rats treated either acutely or repeatedly (five, once daily, inje ctions of 20 mg/kg, i.p.) with morphine. Compared to vehicle pretreated con trols, 18-MG increased the potency of morphine, shifting the dose-response curve to the left, in acute morphine treated rats; however, 18-MG did not a lter the potency of morphine in rats treated repeatedly with morphine. Repe ated morphine administration induced locomotor sensitization in approximate ly 50% of the rats tested; in vehicle pretreated rats, the morphine dose-re sponse curve was shifted to the left in sensitized as compared to non-sensi tized rats. In 18-MG pretreated rats, sensitized and non-sensitized rats re sponded similarly to morphine, revealing a blockade of sensitization by 18- MG. Consistent with this behavioural finding, 18-MG pretreatment completely abolished the sensitized dopamine response in the nucleus accumbens expres sed by rats repeatedly treated with morphine. It is suggested that the pote ntial anti-addictive efficacy of 18-MG might be related to an ability to re store normal functioning to a hypersensitive mesolimbic dopamine system pro duced by previous repeated morphine administration. (C) 2000 Elsevier Scien ce B.V. All rights reserved.