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.