Apomorphine and electrical self-stimulation of rat brain.

The participation of dopamine neurons in reward produced by electrical stimulation of the brain was examined by measuring self-stimulation thresholds after injections of apomorphine, a direct agonist of dopamine receptors. Rats were trained to press a lever to obtain 0.3-s trains of electrical stimulation applied to lateral hypothalamic electrodes in a paradigm where the pulse frequency was decreased every eight stimulations by approximately 20%. The pulse frequency interpolated at 50% of maximum rate was taken as threshold. In a completely within-subject design, five doses of apomorphine from 0.01 to 1.00 mg/kg and the ascorbic acid vehicle were injected in a random order and thresholds were tracked at intervals of 5 min for 2 h postinjection. Low doses from 0.01 to 0.10 mg/kg caused thresholds to increase while the two higher doses, 0.30 and 1.00 mg/kg, caused thresholds to drop; the switch in the direction of the behavioural effect is thought to parallel the shift in apomorphine's action from presynaptic to predominantly postsynaptic activation of dopamine receptors as the concentration of apomorphine increases.