BALB/c mice were unilaterally implanted with a guide-cannula, the tip of which was positioned 1.5 mm above either the amygdala (AMY) or the ventral tegmental area (VTA). On each experimental day, a stainless-steel injection cannula was inserted into these structures in order to compare the self-administration of two doses of morphine (5 ng or 50 ng) in independent groups using a spatial discrimination task in a Y-maze. During the acquisition phase, both AMY and VTA injected mice showed a regular self-administration response at the two doses used. The latency to trigger the injection was short, particularly in the VTA group. Subcutaneous injection of naloxone (4 mg/kg) in trained mice reduced the number of self-administrations to a level near to chance in both groups, which suggests that the drug-seeking behavior observed is effectively dependent on an opiate receptor-mediated mechanism. However the rate of extinction was more rapid in AMY than in VTA injected mice. The 'perseveration' response exhibited by the VTA group during the withdrawal precipitated by naloxone may probably be due to the strong motivational and/or rewarding effect of morphine when injected in this brain structure during acquisition.

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