INFLUENCE OF TETRODOTOXIN AND CALCIUM ON CHANGES IN EXTRACELLULAR DOPAMINE LEVELS EVOKED BY SYSTEMIC NICOTINE

The influence of tetrodotoxin (TTX) and calcium on the increase of ext racellular dopamine (DA) levels in the nucleus accumbens (NAcc), evoke d by the systemic administration of nicotine, cocaine and d-amphetamin e, have been studied in conscious, freely moving rats using in vivo mi crodialysis. TTX (10(-6) M), administered via the dialysis probe, comp letely abolished (P < 0.01) the elevations in extracellular DA, DOPAC and HVA seen following nicotine (0.4 mg/kg SC). The removal of calcium with the inclusion of diaminoethanete-traacetic acid (EDTA 10(-4) M) in the Ringer solution was also associated with inhibition (P < 0.01) of the nicotine-induced changes in these parameters. The systemic admi nistration of cocaine (15 mg/kg IP) and d-amphetamine (0.5 mg/kg SC) c aused elevations in extracellular DA (P < 0.01) accompanied by signifi cant decreases (P < 0.01) in HVA levels. DOPAC levels were also signif icantly (P < 0.01) lowered by d-amphetamine treatment. The presence of TTX and removal of calcium with addition of EDTA completely abolished the changes in NAcc DA and HVA induced by cocaine. TTX had no influen ce on the d-amphetamine evoked responses in NAcc DA. However, the meta bolites, which were markedly reduced by the TTX, were not further decr eased by the systemic administration of d-amphetamine. NAcc DA was sig nificantly (P < 0.01) raised following d-amphetamine in the absence of calcium and presence of EDTA. However, this was significantly (P < 0. 01) attenuated in comparison to that seen in the presence of calcium. The results support the conclusion that, at the dose tested, nicotine evokes increases in extracellular NAcc DA levels by calcium and impuls e-dependent mechanisms. Moreover, the data are also consistent with a partial calcium-dependent component in d-amphetamine-induced stimulati on of this system in vivo.