Direct effect of nicotine on mesolimbic dopamine release in rat nucleus accumbens shell

Nicotine stimulates dopamine (DA) cell firing via a local action at somatodendritic sites in the ventral tegmental area (VTA), increasing DA release in the nucleus accumbens (NAcc). Additionally, nicotine may also modulate DA release via a direct effect in the NAcc. This study examined the contribution of the latter mechanism on NAcc DA release by applying nicotine systemically, as well as locally in the VTA and NAcc shell region in rats. Furthermore, the effect of i.v. nicotine on cell firing rate of dopaminergic neurons in the VTA was measured. Systemic administration of nicotine (0.32 mg/kg s.c.) increased extracellular DA levels in the NAcc to ∼1.5 fold of baseline, while DA levels in the VTA remained unaffected. A similar DA increase was observed after local NAcc infusion of nicotine (1 μM and 10 μM). However, 10–1000-fold higher nicotine concentrations were required in the VTA to produce a comparable 150% increase in extracellular DA levels in the ipsilateral NAcc. Additionally, electrophysiological experiments showed that the dopaminergic firing rate in the VTA showed a trend towards an increase after a nicotine dose of 0.1 mg/kg i.v. Taken together these data indicate that the effects of nicotine on DA release at the level of the NAcc might be more important for the rewarding effects than originally proposed.

► NAcc shell, compared to the VTA, is more sensitive to local nicotine infusion.
► NAcc shell nAChRs might be more important in nicotine induced reward processes than first thought.
► This study shows an elaborate dose-response in the NAcc and VTA, dosing over 4 orders of magnitude.