R-(+)-HA-966, an antagonist for the glycine/NMDA receptor, prevents locomotor sensitization to repeated cocaine exposures.
Repeated administration of cocaine results in a reverse tolerance or sensitization to the locomotor stimulant properties of cocaine. In this study, we examined the effect of an antagonist for the strychinine-insensitive glycine receptor of the NMDA receptor complex, R-(+)-HA-966, on the development of locomotor sensitization to cocaine. Co-administration of R-(+)-HA-966 with repeated cocaine prevented locomotor sensitization to a subsequent challenge dose of cocaine. However, R-(+)-HA-966 (15 mg/kg i.p.) did not attenuate locomotor activation to an acute dose of cocaine (15 mg/kg). These results indicate that the glycine/NMDA receptor is involved in locomotor sensitization to repeated cocaine administration but not in the locomotor activation to the acute stimulant effects of cocaine administration.
Morrow
B A
BA
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520-8066, USA.
Taylor
J R
JR
Roth
R H
RH
D000818:Animals; D001522:Behavior, Animal; D003042:Cocaine / Q000494:pharmacology*; D005625:Frontal Lobe; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013997:Time Factors
D011760:Pyrrolidinones; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; C001369:1-hydroxy-3-amino-2-pyrrolidone; D003042:Cocaine