NMDA-mediated modulation of dopamine release is modified in rat prefrontal cortex and nucleus accumbens after chronic nicotine treatment.

In this study, we investigate the effects of chronic administration of (-)nicotine on the function of the NMDA-mediated modulation of [(3)H]dopamine (DA) release in rat prefrontal cortex (PFC) and nucleus accumbens (NAc). In the PFC synaptosomes NMDA in a concentration-dependent manner evoked [(3)H]DA release in rats chronically treated with vehicle (14 days) with an EC(50) of 13.1 +/- 2.0 microM. The NMDA-evoked overflow of the [(3)H]DA in PFC nerve endings of rats treated with (-)nicotine was significantly lower (-43%) than in vehicle treated rats. The EC(50) was 9.0 +/- 1.4 microM. Exposure of NAc synaptosomes of rats treated with vehicle to NMDA produced an increase in [(3)H]DA overflow with an EC(50) of 14.5 +/- 5.5 microM. This effect was significantly enhanced in chronically treated animals. The EC(50) was 10.5 +/- 0.5 microM. The K(+)-evoked release of [(3)H]DA was not modified by the (-)nicotine administration. Both the changes of the NMDA-evoked [(3)H]DA overflow in the NAc and PFC disappeared after 14 days withdrawal. The results show that chronic (-)nicotine differentially affects the NMDA-mediated [(3)H]DA release in the PFC and NAc of the rat.