Microinjection of the mGluR2/3 agonist, LY379268, into the nucleus accumbens attenuates extinction latencies and the reinstatement of morphine-induced conditioned place preference in rats

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Previous studies indicate that metabotropic glutamate receptor type 2/3 (mGluR2/3) has a key role in the rewarding properties of morphine-induced conditioning place preference (CPP). Group II mGluR2/3 agonists are offered as a drug addiction treatment. The nucleus accumbens (NAc), which is one of the important areas involved in the reward circuitry, also expresses these receptors. In this study, we evaluated the effects of mGluR2/3 agonist, LY379268, on the extinction and reinstatement of morphine-induced CPP, following its microinjection into the NAc. Adult male Wistar rats (220–250 g) were implanted bilaterally by two separate cannulae into the NAc. After the acquisition of morphine CPP, different doses of LY379268 (0.3, 1 and 3 µg/0.5 μl saline) were microinjected into the NAc every day during the extinction period and, in a different set of experiments, on the reinstatement test day, 60 min before the infusion of a priming dose of morphine (1 mg/kg; subcutaneous). Thereafter, the animals were tested for place preference by the Ethovision software. The intra-accumbal injection of the mGluR2/3 agonist, LY379268, significantly decreased the extinction latencies and reinstatement of morphine-induced CPP at higher doses. It seems that the NAc might be a functional region for mGluR2/3 to play a regulatory role for decreasing drug-seeking behavior in rats. Furthermore, it can be said that mGluR2/3 agonists have a potential role in the treatment of drug-seeking behaviors.

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