Attenuation of intravenous amphetamine reinforcement by central dopamine blockade in rats.
Norepinephrine (NE) and dopamine (DA) receptor blockade differentially affected amphetamine self-administration. DA blockade (pimozide, 0.0625 to 0.5 mg/kg, or (+)-butaclamol, 0.0125 to 0.1 mg/kg) caused periods of increased rate of responding for amphetamine which were followed, in the case of higher doses, by response cessation. The response cessation produced by 0.5 mg/kg pimozide was not reversed by non-contingent amphetamine injections until well after the peak effect of the pimozide was over. When access to amphetamine injections was delayed until 4 h after animals received 0.5 mg/kg pimozide, rate of responding was elevated. Thus DA seems to be critically involved in mediation of the reinforcing effects of amphetamine. Alpha-NE blockade with phentolamine (2.5-10 mg/kg) produced dose-related decreases in responding; blockade with phenoxybenzamine (1.25-10 mg/kg) had no effect. Beta-NE blockade with l-propranolol (2.5-10 mg/kg) decreased responding, although probably not through a beta-blocking action. The effects of phentolamine and propranolol do not appear to result from attenuation of the reinforcing effects of amphetamine.
D000818:Animals; D003986:Dibenzocycloheptenes / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D007275:Injections, Intravenous; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010643:Phenoxybenzamine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D010868:Pimozide / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011807:Quinolizines / Q000494:pharmacology; D051381:Rats; D012054:Reinforcement, Psychology
D003986:Dibenzocycloheptenes; D011807:Quinolizines; D010643:Phenoxybenzamine; D010868:Pimozide; D011433:Propranolol; D004298:Dopamine; D010646:Phentolamine