The effects of D-govadine on conditioned place preference with D-amphetamine or food reward
Abstract Tetrahydroprotoberberines (THPB) have a high affinity for dopamine (DA) D1 and D2 receptors and may provide a novel treatment for drug addiction. We assessed the effects of the THPB D -govadine on the acquisition, expression, extinction and reinstatement of D -amphetamine-(1.5mg/kg, i.p.) induced conditioned place preference (CPP). Furthermore, the effects of D -govadine on conditioned association between contextual stimuli and a natural reward were examined using food-induced CPP. In separate experiments, rats received D -govadine (0, 0.5 or 1.0mg/kg, i.p.) before a) each D -amphetamine injection during conditioning, b) expression of amphetamine-induced CPP, c) each extinction session, d) amphetamine-induced reinstatement of CPP, or e) placement into a compartment containing food during conditioning. Although D -govadine had no effect on acquisition of amphetamine CPP, treatment with D -govadine during acquisition dose-dependently extinguished a preference for the amphetamine-associated context more quickly than vehicle treatment. Moreover, D -govadine treatment facilitated the extinction of amphetamine CPP when given repeatedly throughout the extinction phase. Although the expression of amphetamine CPP was not affected by D -govadine administered prior to the expression test, amphetamine-induced reinstatement of CPP following an extinction period was blocked by D -govadine (1.0mg/kg). The intermediate dose of D -govadine blocked the acquisition of food CPP, whereas the high dose facilitated extinction of this preference as compared to vehicle-treated animals. Therefore, D -govadine attenuates the maintenance of conditioned associations between contextual stimuli and amphetamine or food reward, as well as amphetamine-induced reinstatement of drug seeking behaviour. As such, D -govadine may be a candidate for further development as a pharmacological treatment of psychostimulant drug dependence. Highlights D -Govadine facilitates the rate of extinction of amphetamine CPP when administered either during the conditioning or extinction phase. D -Govadine blocks the acquisition of food CPP when administered during the conditioning phase. D -Govadine blocks the amphetamine-induced reinstatement of amphetamine CPP. These effects suggest that D -govadine may have differential effects on the acquisition of conditioned associations and extinction learning, and has broad effects on the reward-context associations.
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