D₁ and D₂ dopamine receptors independently regulate spontaneous blink rate in the vervet monkey

Previous studies have revealed the involvement of a dopaminergic link in the regulation of spontaneous eye blink rate in primates. Based on the effect of dopamine D₂ receptor-selective drugs and the anecdotal failure of the partial D₁ agonist, SKF 38393, to alter blink rate in monkeys, it was assumed that D₁ dopamine receptors did not control blink rate. The recent availability of dihydrexidine, a full D₁ agonist, prompted us to re-evaluate the role of D₁ and D₂ receptors in the regulation of blink rate. African green monkeys (n = 5) were used in all studies. Dihydrexidine produced a rapid and dose-dependent (up to 1 mg/kg, i.m.) increase in blink rate. The elevation in blink rate elicited by 0.3 mg/kg dihydrexidine was completely reversed by prior administration of a specific D₁ antagonist, SCH 23390 (0.01 mg/kg, i.m.), but was unaffected by prior administration of a specific D₂ antagonist, remoxipride (1 mg/kg, i.m.). Treatment with the specific D₂ agonist, (+)-4-propyl-9-hydroxynaphthoxazine, led to a rapid and dose- dependent (up to 0.01 mg/kg, i.m.) increase in blink rate. The raised blink rate produced by (+)-4-propyl-9-hydroxynaphthoxazine (0.001 mg/kg) was abolished by pretreatment with remoxipride, but was not influenced by pretreatment with SCH 23390. These data indicate that spontaneous blink rate in the primate can be regulated by both D₁ and D₂ dopamine receptors. Furthermore, the receptor subtypes appear to affect blink rate in the same direction, yet function independently. Measurement of blink rate may provide a noninvasive method to assess the potency and selectivity of dopamine agonists and antagonists in primates.