Role of noradrenergic and dopaminergic processes in amphetamine self-administration.
Dogs were trained to intravenously self-administered d-amphetamine (0.05 mg/kg/infusion) until a stable intake per 4 hr daily session was achieved. When the dogs were given noncontingent infusions of d-amphetamine in varying amounts o% to 100% of the baseline intake) immediately prior to the session, they decreased their self-administration response rate appropriately so that total drug intake remained constant. However, there were not changes in subsequent responding for d-amphetamine following pretreatment with either the noradrenergic agonist methoxamine (0.5-2.0 mg/kg) or the noradrenergic antagonist phenoxybenzamine (1-8 mg/kg).  Additionally, responding was not maintained when methoxamine (0.05 mg/kg/infusion) was substituted for d-amphetamine. In contrast, pretreatment with either the dopaminergic antagonist pimozide (5-40 mug/kg) or chlorpromazine (0.25-2.0 mg/kg) produced dose-dependent increases in the number of self-administered d-amphetemine infustions. These data suggest that noradrenergic neurotransmission is not responsible for d-amphetamine self-administration, but an intact dopaminergic system does appear to be important.
D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology; D003913:Dextroamphetamine / Q000008:administration & dosage*; D004285:Dogs; D004298:Dopamine / Q000502:physiology*; D005260:Female; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009638:Norepinephrine / Q000502:physiology*; D010643:Phenoxybenzamine / Q000494:pharmacology; D010868:Pimozide / Q000494:pharmacology; D012646:Self Administration
D010643:Phenoxybenzamine; D010868:Pimozide; D008729:Methoxamine; D003913:Dextroamphetamine; D002746:Chlorpromazine; D004298:Dopamine; D009638:Norepinephrine