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 10 mg/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, 10 mg/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.

► GYKI 52466 is a systemically active non-competitive AMPA receptor antagonist.
► GYKI 52466 (1, 3, 10 mg/kg) did not alter cocaine self-administration.
► GYKI 52466 (3, 10 mg/kg) did not alter cocaine-evoked reinstatement of drug seeking.
► These findings suggest that GYKI 52466 has low potential for cocaine addiction treatment.