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

Neuroscience. 1999 May;90(2):447-55. doi: 10.1016/s0306-4522(98)00466-7.


In this study, we describe a model of opiate sensitization characterized by a brief schedule of treatment with repeated morphine administrations. In this model, we investigated the changes produced by repeated morphine treatment on dopamine transmission at the level of the two major terminal dopaminergic 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 strong behavioral sensitization accompanied by increased stimulation of dopamine transmission in the core of the nucleus accumbens and in the caudate-putamen, and by a decreased stimulation of dopamine transmission in the shell of the nucleus accumbens, as compared to control rats. Moreover, we administered 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 psychostimulants in conditions independent of the context. In the present study, we did not observe either behavioral or biochemical sensitization to amphetamine and to cocaine in rats sensitized to morphine. These results suggest that rats behaviorally sensitized to morphine show opposite changes in the stimulant effect of morphine in the nucleus accumbens shell and core and in the dorsal caudate-putamen. Moreover, this study suggests that sensitization of the dopamine system to a given agent does not necessarily extend to drugs of abuse of different pharmacological classes.

MeSH terms

  • Amphetamine / pharmacology
  • Animals
  • Catalepsy
  • Caudate Nucleus / drug effects
  • Caudate Nucleus / metabolism
  • Caudate Nucleus / physiopathology*
  • Cocaine / pharmacology
  • Dopamine / metabolism*
  • Drug Interactions
  • Grooming
  • Male
  • Microdialysis
  • Morphine / pharmacology*
  • Morphine Dependence / metabolism
  • Morphine Dependence / physiopathology*
  • Motor Activity / drug effects
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism
  • Nucleus Accumbens / physiopathology*
  • Putamen / drug effects
  • Putamen / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Stereotyped Behavior / drug effects
  • Substance Withdrawal Syndrome / metabolism
  • Substance Withdrawal Syndrome / physiopathology


  • Morphine
  • Amphetamine
  • Cocaine
  • Dopamine