Infusions of serotonin (5X10 -6 - 5X10 -5) into the nucleus accumbens increased dopamine (DA) overflow in a concentration-dependent fashion. These effects of 5-HT were blocked by the specific 5-HT3 receptor blocker MDA 72222 which also attenuated the effects of cocaine on DA overflow. Injections of mu, kappa, and delta selective opioid peptides into the VTA increased feeding and locomotor behaviors. The mu and delta opioid peptides produced a more pronounced rise in extracellular DA than dynorphin, the kappa ligand. Focal applications of cocaine produced a concentration-dependent increase in 5-HT in the n. accumbens, striatum, and frontal cortex. The striatum appeared to be the most responsive. Basal levels of 5-HT were the highest in the n. accumbens and lowest in the frontal cortex. Cocaine, WIN-065-02 and nomifensine enhance mesolimbic DA function at substantially lower occupancy of the DA transporter than does GBR12909. Pretreatment with 5-HT3 blockers attenuated increases in mesolimbic and nigrostriatal DA overflow induced by ethanol.
