Pharmacological activity profiles of dopamine D-1 and D-2 reception agonists and antagonists on striatal neuronal activity and the response to dexamphetamine in freely moving rats

Abstract

1. 1. The effects of dopamine D-1 and D-2 receptor agonists and antagonists were investigated by recording extracellular striatal action potentials in freely moving rats. Dopamine receptor antagonist effects were also evaluated on dexamphetamine-induced excitation of striatal neurons. 2. 2. Striatal neurons responded to SKF 38393, a D-1 agonist, with dose-dependent reductions in activity. At a 2.0 mg/kg dose neuronal activity decreased to 50% of control values. 3. 3. The D-1 antagonist, SCH 23390, at a dose of 4.0 mg/kg decreased striatal neuronal activity by more than 50% and also effectively blocked the effects of 2.5 mg/kg dexamphetamine. 4. 4. LY 171555, a D-2 agonist, at 1.0 or 2.5 mg/kg, did not significantly increase striatal neuronal activity. Although behavioral activation was noted, the neuronal response at the high dose was biphasic with inhibition predominant. 5. 5. The D-2 antagonists haloperidol and sulpiride decreased striatal neuronal activity in a dose-dependent manner and also effectively antagonized the effects of dexamphetamine. The D-2 antagonist, RO 22-1319, at a dose of 2.0 mg/kg completely antagonized increases in striatal neuronal activity after dexamphetamine. 6. 6. These findings suggest that dexamphetamine-induced increases in striatal neuronal activity are due to either stimulation of both D-1 and D-2 receptors, or alternatively, a third dopamine receptor subtype sensitive to both D-1 and D-2 antagonists but not agonists. Furthermore, the concept of specific D-1 and D-2 receptor agonists may require revision as neither SKF 38393 or LY 171555 increased striatal neuronal activity.