GABAB receptors within the central nucleus of amygdala may involve in the morphine-induced incentive tolerance in female rats.

OBJECTIVES: Central nucleus of amygdala (CeA) is the most important region for morphine-induced reward, and GABAergic system plays an important role on morphine reinforcement. The influence of CeA administration of GABAB receptor agonist and antagonist on the expression and acquisition of morphine-induced incentive tolerance using conditioned place preference (CPP) paradigm was investigated in the present study. Our purpose was to evaluate the role of CeA GABAB receptors in morphine tolerance.

MATERIALS AND METHODS: Seven days after surgery and cannulation, the experiments were begun. Subcutaneous (SC) injections of morphine induced CPP. Administration of one daily dose of morphine (12.5 mg/kg) for 3 days in order to develop tolerance to the drug reduced the conditioning induced by morphine (7.5 mg/kg, SC). GABAB receptor agonist, baclofen (1.5, 6 and 12 µg/rat) or GABAB receptor antagonist, CGP35348 (1.5, 6 and 12 µg/rat) were injected into the CeA 5 min before the experiments in the test day (expression of tolerance) or 5 min before each injection of morphine (12.5 mg/kg) (acquisition of tolerance).

RESULTS: It was shown that injections of baclofen (1.5 and 12 µg/rat) reduced acquisition, whereas the dose of 6 µg/rat of the drug exacerbated the acquisition of morphine tolerance. Baclofen at all doses significantly increased the expression of tolerance to morphine. Administration of CGP35348 (1.5, 6 and 12 µg/rat) reduced the acquisition and expression of morphine tolerance.

CONCLUSION: These results confirmed the importance of GABAB receptors with in the CeA in morphine tolerance in female rats.