Reciprocal changes in dopamine responsiveness in the nucleus accumbens shell and core and in the dorsal caudate-putamen in rats sensitized to morphine

In this study, we describe a model of opiate sensitization characterized by a brief schedule of treatment with repeated morphine administrations. In t his model, we investigated the changes produced by repealed morphine treatm ent on dopamine transmission at the level of the two major terminal dopamin ergic areas, the dorsolateral caudate-putamen and the nucleus accumbens in its two subdivisions, the shell and the core. Rats were treated twice a day for three days with increasing doses of morphine (10, 20 and 40 mg/kg, s.c .) or with saline. After 15 days of withdrawal, rats were challenged with 1 and 5 mg/kg (s.c.) of morphine, and dopamine transmission was monitored by microdialysis. In this model, we show that repeated morphine produces a st rong behavioral sensitization accompained by increased stimulation of dopam ine transmission in the core of the nucleus accumbens and in the caudate-pu tamen, and by a decreased stimulation of dopamine transmission in the shell of the nucleus accumbens, as compared to control rats. Moreover, we admini stered to these animals amphetamine (0.5 mg/kg, s.c.) and cocaine (10 mg/kg , i.p.) to assess whether cross-sensitization occurs between opiates and ps ychostimulants in conditions independent of the context. In the present stu dy, we did not observe either behavioral or biochemical sensitization to am phetamine and to cocaine in rats sensitized to morphine. These results suggest that rats behaviorally sensitized to morphine show op posite changes in the stimulant effect of morphine in the nucleus accumbens shell and core and in the dorsal caudate-putamen, Moreover, this study sug gests that sensitization of the dopamine system to a given agent does not n ecessarily extend to drugs of abuse of different pharmacological classes. ( C) 1999 IBRO. Published by Elsevier Science Ltd.