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 reevaluate 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.
Elsworth
J D
JD
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
Lawrence
M S
MS
Roth
R H
RH
Taylor
J R
JR
Mailman
R B
RB
Nichols
D E
DE
Lewis
M H
MH
Redmond
D E
DE
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001767:Blinking / Q000187:drug effects / Q000502:physiology*; D002522:Chlorocebus aethiops; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists; D004305:Dose-Response Relationship, Drug; D008297:Male; D010078:Oxazines / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D017330:Remoxipride; D013997:Time Factors
D001549:Benzamides; D001552:Benzazepines; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D010078:Oxazines; D010617:Phenanthridines; D011954:Receptors, Dopamine; D017330:Remoxipride; C042631:naxagolide; C061532:dihydrexidine