Does adenosine receptor blockade mediate caffeine-induced rotational behavior?
Caffeine, a competitive antagonist at adenosine receptors, produces contralateral turning in rats with unilateral 6-hydroxydopamine-induced lesions of the nigrostriatal pathway. Adenosine A2a and dopamine D2 receptors are negatively coupled in the striatum; blockade of these adenosine receptors is a possible mechanism of caffeine-induced rotational behavior. The present study had three objectives: 1) to evaluate the role of adenosine receptor blockade in the rotational behavior elicited by caffeine in rats. This was done by determining the dose-response functions for turning behavior induced by caffeine, by six other methylxanthine adenosine antagonists and by CGS 15943 [9-chloro-2-(2-furanyl)-5,6-dihydro-1,2,4-triazolo[1,5- c]quinazolin-5-imine], a potent nonxanthine adenosine antagonist; 2) to determine if selective dopamine receptor antagonist block caffeine-induced rotational behavior; and 3) to determine if tolerance develops to caffeine-induced rotational behavior as it does to caffeine-induced stimulation of locomotor activity. Theophylline, paraxanthine, caffeine and beta-hydroxytheophylline, in that order of potency, produced contralateral turning, but 3-isobutyl-1-methylxanthine, 8-chlorotheophylline, theobromine and CGS 15943 did not. Caffeine-induced turning was blocked by eticlopride (dopamine D2 antagonist), but not by SCH 23390 [R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H- 3-benzazepine] (dopamine D1 receptor antagonist), suggesting involvement of the dopamine D2 receptor. Rats treated chronically with an p.o. caffeine solution (75 mg/kg/day average intake) were tolerant to turning induced by caffeine and cross-tolerant to turning induced by theophylline.(ABSTRACT TRUNCATED AT 250 WORDS)
Garrett
B E
BE
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia, USA.
Holtzman
S G
SG
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002110:Caffeine / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004361:Drug Tolerance; D008297:Male; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors
D065127:Dopamine D2 Receptor Antagonists; D058915:Purinergic P1 Receptor Antagonists; D017447:Receptors, Dopamine D1; D002110:Caffeine