Cocaine-taking and cocaine-seeking behaviors in rats remain stable after systemic administration of GYKI 52466: a non-competitive AMPA receptor antagonist.
Given the posited role of enhanced AMPA-mediated synaptic transmission in relapse to drug seeking, we investigated whether systemic administration of the AMPA receptor antagonist GYKI 52466 inhibits cocaine-taking and cocaine-seeking behavior in rats. Rats were trained to self-administer cocaine until stable self-administration was achieved. Effects of GYKI 52466 (1, 3, or 10mg/kg, i.v.) on cocaine self-administration were assessed. Animals were allowed to re-establish stable cocaine self-administration and were then behaviorally extinguished from drug taking. The effects of GYKI 52466 (3, 10mg/kg, i.v.) on cocaine-induced reinstatement of drug-seeking behavior were assessed. We found that GYKI 52466 failed to inhibit cocaine-taking and cocaine-seeking in both the self-administration and reinstatement paradigms. We suggest that although AMPA receptors may be involved in cocaine reward and addiction, the AMPA receptor antagonist GYKI 52466 has low therapeutic potential for cocaine addiction treatment.
National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD 21224, USA. ratika.srivastava@nih.gov
Ratika
R
Srivastava
Zheng-Xiong
ZX
Xi
Eliot L
EL
Gardner
D000818:Animals; D001569:Benzodiazepines / Q000008:administration & dosage / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D012646:Self Administration
D018091:Receptors, AMPA; C061950:GYKI 52466; D001569:Benzodiazepines; D003042:Cocaine