Mesolimbic sites mediate the discriminative stimulus effects of morphine

The neuroanatomical basis of opiate addiction has been studied using a variety of behavioural techniques. Mesolimbic structures such as the ventral tegmental area and nucleus accumbens appear to be critical in mediating the expression of rewarding effects of opiates. However, the role of these brain structures in mediating the discriminative stimulus effects have not been fully examined. The aim of the present study was to investigate the role of the ventral tegmental area and the nucleus accumbens in a two-lever operant drug discrimination paradigm. Male Wistar rats were trained to discriminate morphine (3.0 mg/kg s.c.) from saline with a fixed ratio schedule of food reinforcement (FR10). Once rats had acquired the discrimination, a randomised sequence of morphine microinjections (1-10 micrograms) were evaluated. Subsequently, tests with morphine (1.0-10.0 mg/kg s.c.) administered systemically were performed to confirm the integrity of the discrimination. Small doses of morphine (1-3 micrograms) administered into the ventral tegmental area proved sufficient to produce generalisation to the systemic cue, whereas similar injections into the nucleus accumbens produced only partial generalisation. Furthermore, these intra-nucleus accumbens injections (3-10 micrograms) produced significant increases in the latency to complete the first ratio. Similar doses of morphine administered into the striatum failed to show generalisation. These results demonstrate that activation of opioid receptors located within mesolimbic structures mediate, in part, the discriminative stimulus effects of morphine. Furthermore, the finding that the discriminative stimulus effects and rewarding effects share common neural pathways suggest a possible linkage between the two stimulus properties.