Effect of Glycogen Synthase Kinase-3 Inhibition on the Acquisition and Expression of Cocaine-Cue Conditioned Activity and Spontaneous Locomotion in Rodents

Abstract

Pairing environmental stimuli with pro-dopaminergic drugs can produce conditioned effects on locomotor behaviour in rodents, an effect that is used to model incentive learning and drug craving in laboratory animals. One of the targets of dopamine signaling is glycogen synthase kinase-3 (GSK-3), a nearly constitutively active enzyme involved in a variety of cellular activities and signaling pathways. Recently, GSK-3 has been shown to be modulated by activity at the dopamine D2 and D3 receptors, both of which have been implicated in the acquisition and expression of conditioned activity. Here, it was hypothesized that the selective GSK-3 inhibitor, A-1070722 (Abbott Laboratories, Ludwigshafen, Germany), would block the acquisition and expression of cocaine-cue conditioned activity in Wistar rats. Results indicated a block of the expression, but not acquisition, of conditioned activity at 10 and 20 mg/kg doses of A-1070722, but not 0, 1, or 5 mg/kg doses. The 10 mg/kg dose also appeared to decrease spontaneous locomotion, suggesting that the effect of A-1070722 on the expression of conditioned activity may be due an effect on locomotor behaviour more generally, rather than being due to a selective attenuation of the expression of incentive learning produced by cocaine-associated environmental stimuli.