DEPRESSION OF MESOLIMBIC DOPAMINE TRANSMISSION AND SENSITIZATION TO MORPHINE DURING OPIATE ABSTINENCE

被引:206
作者
ACQUAS, E [1 ]
DICHIARA, G [1 ]
机构
[1] UNIV CAGLIARI,INST EXPTL PHARMACOL & TOXICOL,V LE DIAZ 182,I-09126 CAGLIARI,ITALY
关键词
DOPAMINE; MICRODIALYSIS; ADDICTION; MORPHINE; OPIATES; DEPENDENCE; WITHDRAWAL;
D O I
10.1111/j.1471-4159.1992.tb10033.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
To investigate the role of mesolimbic dopamine (DA) in the mechanism of drug dependence, extracellular DA was monitored by transcerebral dialysis in the caudal nucleus accumbens under basal conditions and after challenge with morphine (5 mg/kg s.c.) in control rats and in rats made dependent on and then deprived of morphine. Withdrawal from morphine resulted in a marked reduction of extracellular DA concentrations from control values at 1, 2, 3, and 5 days of withdrawal. After 7 days of withdrawal, DA output was less, but still significantly, reduced. Challenge with morphine resulted in stimulation of DA output in controls (maximum, 35%), no effect on the first day of withdrawal, and stimulation similar to controls' on days 2 and 7 of withdrawal. On day 5 and, particularly, on day 3 of withdrawal, morphine-induced stimulation of DA output was markedly potentiated (maximum, 100 and 160%, respectively). Changes in the sensitivity of DA transmission to morphine challenge were associated with changes in the behavioral stimulant effects of morphine, with tolerance on day 1 and marked sensitization on days 3 and 5 but also on day 7, when morphine-induced stimulation of transmission was no longer potentiated. The results indicate that repeated morphine administration induces a state of dependence in DA neurons and a short-lasting tolerance followed by an increased sensitivity to its stimulant effects on DA transmission. These changes might play an important role in the development of opiate addiction and in the maintenance of opiate self-administration in dependent subjects.
引用
收藏
页码:1620 / 1625
页数:6
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