Discriminative effects of CGS 15943, a competitive adenosine receptor antagonist, have a dopamine component in monkeys.
9-Chloro-2-(2-furyl)[1,2,4]triazolol[1,5-c]quinazolin-5-amin e (CGS 15943), like caffeine, is an antagonist at adenosine A1 and A2A receptors and a behavioral stimulant in animals. The two drugs have overlapping discriminative effects. Enhancement of dopamine-mediated neurotransmission appears to contribute to the behavioral effects of caffeine. This study was conducted to determine if there is a dopamine component to the discriminative effects of CGS 15943. Squirrel monkeys discriminating between i.m. injections of 1.0 mg/kg CGS 15943 and vehicle generalized dose-dependently and completely to eight dopamine receptor agonists that encompass a variety of mechanisms and sites of action, both pre- and postsynaptic. The discriminative effects of the training dose of CGS 15943 were blocked dose-dependently and completely by the dopamine receptor antagonists R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzaz epine (SCH 23390; D1) and eticlopride (D2). Thus, the discriminative effects of CGS 15943 have a dopamine component that appears to be mediated by both the D1 and D2 families of dopamine receptors. The monkeys also generalized to selective inhibitors of the neuronal transporters of norepinephrine (nisoxetine) and serotonin (fluoxetine), indicating that monoamines other than dopamine also contribute to the discriminative effects of CGS 15943.
Holtzman
S G
SG
Rollins Research Center, Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322-3090, USA. sholtzm@emory.edu
D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D005795:Generalization, Stimulus / Q000187:drug effects; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000378:metabolism; D010622:Phencyclidine / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D011799:Quinazolines / Q000494:pharmacology*; D043705:Receptor, Adenosine A2A; D017982:Receptors, Biogenic Amine / Q000037:antagonists & inhibitors; D012453:Saimiri; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology*
D003042:Cocaine; D003913:Dextroamphetamine; D004298:Dopamine; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D009020:Morphine; D009638:Norepinephrine; D010622:Phencyclidine; D058915:Purinergic P1 Receptor Antagonists; D011799:Quinazolines; D043705:Receptor, Adenosine A2A; D017982:Receptors, Biogenic Amine; D017367:Selective Serotonin Reuptake Inhibitors; D014230:Triazoles; C052410:9-chloro-2-(2-furyl)-(1,2,4)triazolo(1,5-c)quinazolin-5-imine