INCREASE OF EXTRACELLULAR DOPAMINE IN THE MEDIAL PREFRONTAL CORTEX DURING SPONTANEOUS AND NALOXONE-PRECIPITATED OPIATE ABSTINENCE

Abstinence from chronic morphine has been shown to reduce extracellula r dopamine in the nucleus accumbens as measured by brain microdialysis (Acquas et al. 1991). In the present study, we investigated if simila r changes take place in the prefrontal cortex. Withdrawal from a sched ule of increasing doses of morphine administered intraperitoneally twi ce a day for 9 days up to a daily dose of 60 mg/kg resulted in doublin g of basal extracellular concentrations of dopamine in the prefrontal cortex and in a mild withdrawal syndrome (ptosis, piloerection, hunche d-back posture). Administration of a low dose of naloxone (0.5 mg/kg S C) to rats withdrawn from chronic morphine resulted in a full withdraw al syndrome with wet dog shakes and diarrhoea and an increase of extra cellular dopamine that peaked at 40 min and returned to the pre-naloxo ne values by 80 min. The results show that dopamine neurotransmission in the medial prefrontal cortex responds to opiate withdrawal in a man ner opposite to dopamine transmission in the nucleus accumbens and ind icate that the dopamine system is affected by abstinence in a topograp hically specific manner, consistent with a different functional role o f mesocortical as compared to mesolimbic dopamine systems.