Interactions between the mGluR2/3 agonist, LY379268, and cocaine on in vivo neurochemistry and behavior in squirrel monkeys

Abstract

Recent evidence indicates that group II metabotropic glutamate receptors (mGluR2 and mGluR3) may play a role in the pathology of cocaine addiction. The purpose of the current study was to determine the effects of the mGluR2/3 agonist, LY379268, on cocaine-induced changes in DA neurochemistry in nonhuman primates. Furthermore, the current study aimed to determine if changes in DA neurochemistry would correlate with LY379268-induced changes in the behavioral effects of cocaine. In vivo microdialysis was conducted in conscious squirrel monkeys ( n = 4) in order to monitor cocaine-induced changes in extracellular DA in the caudate nucleus. Separate groups of subjects were trained on a fixed-interval schedule of stimulus termination ( n = 4) or a second-order schedule of cocaine self-administration ( n = 5) to characterize the behavioral-stimulant and reinforcing effects, respectively. LY379268 significantly attenuated cocaine-induced increases in DA. LY379268 also significantly attenuated cocaine-induced behavioral-stimulant effects following a short pretreatment time, but not following a longer pretreatment time. Cocaine self-administration was significantly attenuated but only at an intermediate pretreatment dose of LY379268. Moreover, reinstatement of previously extinguished cocaine self-administration was not significantly attenuated by LY379268. Hence, drug interactions on neurochemistry did not correlate well with behavioral measures.