title: 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.
authors.affiliation: Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 3402-2215 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada. Electronic address: mayan0324@gmail.com.
authors.forename: Maya O
authors.initials: MO
authors.lastname: Nesbit
authors.affiliation: Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 3402-2215 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada. Electronic address: carine.dias@gmail.com.
authors.forename: Carine
authors.initials: C
authors.lastname: Dias
authors.affiliation: Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 3402-2215 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada. Electronic address: aphillips@psych.ubc.ca.
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Phillips
mesh_terms: D019969:Amphetamine-Related Disorders / Q000188:drug therapy; D000818:Animals; D001600:Berberine Alkaloids / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects*; D003913:Dextroamphetamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000187:drug effects; D005502:Food; D008297:Male; D009042:Motivation / Q000187:drug effects; D011619:Psychotropic Drugs / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D012201:Reward; D013037:Spatial Behavior / Q000187:drug effects
chemical_list: D001600:Berberine Alkaloids; D000697:Central Nervous System Stimulants; D011619:Psychotropic Drugs; C103305:govadine; D003913:Dextroamphetamine
keywords: Addiction; Associative learning; Conditioned place preference; Tetrahydroprotoberberine; d-Amphetamine; d-Govadine