Excitatory amino acid receptor antagonist kynurenic acid attenuates rewarding potential of morphine.
The effect of the non-selective antagonist of excitatory amino acid receptors kynurenic acid (50, 100 and 150 mg/kg, i.p.) on morphine-derived reward was studied in rats. Kynurenic acid dose dependently blocked the acquisition of morphine conditioned place preference when injected before conditioning. The expression of the previously established conditioned behavior was also blocked by the pretreatment with kynurenic acid (at the doses which do not reduce spontaneous locomotor activity) before testing. In the control experiments we failed to find that kynurenic acid alone exerts positive place preference conditioning or aversion. Kynurenic acid also attenuated the morphine-induced facilitation of responding in the intracranial self-stimulation test, causing a decrease in response rate and an increase in threshold current intensity. This effect was observed with doses at which kynurenic acid does not affect responding in the self-stimulation test by itself.
Bespalov
A
A
Department of Pharmacology, Pavlov Medical University, St.-Petersburg, Russian Federation.
Dumpis
M
M
Piotrovsky
L
L
Zvartau
E
E
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004594:Electrophysiology; D005629:Frozen Sections; D007274:Injections, Intraperitoneal; D007736:Kynurenic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008839:Microelectrodes; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects
D016194:Receptors, N-Methyl-D-Aspartate; D009020:Morphine; D007736:Kynurenic Acid