Dopamine release and metabolism in nucleus accumbens and striatum of morphine-tolerant and nontolerant rats.

Morphine administered at high doses produces a biphasic locomotor effect, characterized by an initial locomotor depression, followed a short time later by hyperlocomotion. Prior exposure to morphine produces tolerance to the motor-depressive effects and sensitization to the motor-activating effects of morphine. Little is known of the neurochemical changes that occur to produce tolerance and sensitization to morphine. In the present study, we developed a morphine pretreatment regimen in rats that produced both tolerance and sensitization to a high (30 mg/kg) dose of morphine. Using in vivo microdialysis, we then measured dopamine (DA), dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) release in the nucleus accumbens (NAC) and striatum (STR) in morphine- and saline-pretreated rats after acute morphine administration. In morphine-tolerant/sensitized rats, basal DA concentrations in the NAC were higher and levels of DOPAC and HVA in the NAC after acute morphine injection were greater compared to controls. These results suggest that the NAC, but not the STR, may be important in mediating tolerance and sensitization to opiates.