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Effects of dopamine D1 ligands on eye blinking in monkeys: efficacy, antagonism, and D1/D2 interactions.
J Pharmacol Exp Ther. 2004 Dec; 311(3):1008-15.JP

Abstract

Dopamine D1 ligands have been classified and ordered according to efficacy in both in vitro and in vivo studies. In the present experiments, dopamine D1 ligands reported to differ in in vitro efficacy were evaluated for efficacy-related effects on eye blinking in squirrel monkeys. Additional comparisons were made with the effects of D2 receptor agonists and indirect dopamine agonists. The results show that D1 agonists increased eye blinking in an efficacy-related manner, whereas the D1 receptor blocker SCH 39166 [(-)-trans-6,7,7alpha,8,9,13beta-hexahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo[d]naphtho[2,1-b]azepine] only decreased rates of eye blinking. D1 high-efficacy agonists induced rates of eye blinking that were 2- to 3-fold greater than observed with dopamine D2 agonists and indirect agonists. In drug combination experiments, increases in eye blinking induced by the D1 high-efficacy agonist R-(+)-6-Br-APB [R-(+)-6-bromo-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide] were antagonized by both the D1 antagonist SCH 39166 and the lower efficacy agonist SKF 83959 [6-chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide], consistent with dopamine D1 receptor mediation of these behavioral effects. The dopamine D2 agonist (+)-PHNO [(+)-N-propyl-hydroxynaphthoxazine], which selectively activates dopamine D2 receptors, also attenuated D1 agonist-induced increase in eye blinking, suggesting that D2 receptor actions may inhibit D1-mediated increases in eye blinking. Overall, eye blink rate appears to be a robust behavioral measure that can be used to measure changes in dopaminergic D1 signaling and as a functional assay of agonist efficacy at dopamine D1 receptors.

Authors+Show Affiliations

McLean Hospital, 115 Mill Street, Belmont MA 02478, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15292458

Citation

Jutkiewicz, Emily M., and Jack Bergman. "Effects of Dopamine D1 Ligands On Eye Blinking in Monkeys: Efficacy, Antagonism, and D1/D2 Interactions." The Journal of Pharmacology and Experimental Therapeutics, vol. 311, no. 3, 2004, pp. 1008-15.
Jutkiewicz EM, Bergman J. Effects of dopamine D1 ligands on eye blinking in monkeys: efficacy, antagonism, and D1/D2 interactions. J Pharmacol Exp Ther. 2004;311(3):1008-15.
Jutkiewicz, E. M., & Bergman, J. (2004). Effects of dopamine D1 ligands on eye blinking in monkeys: efficacy, antagonism, and D1/D2 interactions. The Journal of Pharmacology and Experimental Therapeutics, 311(3), 1008-15.
Jutkiewicz EM, Bergman J. Effects of Dopamine D1 Ligands On Eye Blinking in Monkeys: Efficacy, Antagonism, and D1/D2 Interactions. J Pharmacol Exp Ther. 2004;311(3):1008-15. PubMed PMID: 15292458.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of dopamine D1 ligands on eye blinking in monkeys: efficacy, antagonism, and D1/D2 interactions. AU - Jutkiewicz,Emily M, AU - Bergman,Jack, Y1 - 2004/08/03/ PY - 2004/8/5/pubmed PY - 2005/1/14/medline PY - 2004/8/5/entrez SP - 1008 EP - 15 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 311 IS - 3 N2 - Dopamine D1 ligands have been classified and ordered according to efficacy in both in vitro and in vivo studies. In the present experiments, dopamine D1 ligands reported to differ in in vitro efficacy were evaluated for efficacy-related effects on eye blinking in squirrel monkeys. Additional comparisons were made with the effects of D2 receptor agonists and indirect dopamine agonists. The results show that D1 agonists increased eye blinking in an efficacy-related manner, whereas the D1 receptor blocker SCH 39166 [(-)-trans-6,7,7alpha,8,9,13beta-hexahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo[d]naphtho[2,1-b]azepine] only decreased rates of eye blinking. D1 high-efficacy agonists induced rates of eye blinking that were 2- to 3-fold greater than observed with dopamine D2 agonists and indirect agonists. In drug combination experiments, increases in eye blinking induced by the D1 high-efficacy agonist R-(+)-6-Br-APB [R-(+)-6-bromo-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide] were antagonized by both the D1 antagonist SCH 39166 and the lower efficacy agonist SKF 83959 [6-chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide], consistent with dopamine D1 receptor mediation of these behavioral effects. The dopamine D2 agonist (+)-PHNO [(+)-N-propyl-hydroxynaphthoxazine], which selectively activates dopamine D2 receptors, also attenuated D1 agonist-induced increase in eye blinking, suggesting that D2 receptor actions may inhibit D1-mediated increases in eye blinking. Overall, eye blink rate appears to be a robust behavioral measure that can be used to measure changes in dopaminergic D1 signaling and as a functional assay of agonist efficacy at dopamine D1 receptors. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/15292458/Effects_of_dopamine_D1_ligands_on_eye_blinking_in_monkeys:_efficacy_antagonism_and_D1/D2_interactions_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=15292458 DB - PRIME DP - Unbound Medicine ER -