Differential effects of direct and indirect dopamine agonists on eye blink rate in cynomolgus monkeys

Spontaneous eye blink rate was assessed in cynomolgus monkeys treated intramuscularly with the high-efficacy dopamine (DA) agonists, (-)-apomorphine, naxagolide, PD 128,907, 2-(N-phenylethyl-N-propyl)amino-5-hydroxytetralin (+/-)-PPHT, quinpirole, SKF 81297 and SKF 82958; the low-efficacy DA agonists, (-)-3-PPP, roxindole, SDZ 208-912, SKF 75670 and terguride; and the indirect DA agonists, d-amphetamine, cocaine, GBR 12935 and methylphenidate. All of the direct DA agonists, with the exception of the partial agonists SDZ 208-912 and terguride, produced significant, dose-related elevations in blink rate. In contrast, none of the indirect agonists increased blink rates when administered over a relatively wide, behaviorally active dose range. These differences suggest either that indirect agonists do not interact with mechanisms involved in eye blinking, or that they have other effects which prevent blink-rate increases. The latter does not appear to be the case because cocaine failed to alter the blink rate-increasing effects of the D1 agonist, SKF 81297, which suggests that indirect agonists do not mask their own ability to induce blinking. Overall, the results further characterize the involvement of DA receptors in the mediation of spontaneous eye blinks, reveal differential effects of direct and indirect agonists and suggest new directions for research into the neuroanatomical basis of DA-mediated spontaneous eye blinks.