Nicotinic ligands modulate ethanol-induced dopamine function in mice

The aim of the present study was to examine the effects of two neuronal nicotinic acetylcholine receptor ligands on acute ethanol-induced dopamine (DA) function in the C57BL/6J mouse ventral striatumusing an ex vivo assay and high-performance liquid chromatography coupled with electrochemicaldetection. Acute systemic injection of ethanol (2.5 g/kg) significantly increased the DA and dihydroxyphenylacetic acid (DOPAC) content in the ventral striatum. Pretreatment with lobeline (1 or 10 mg/kg) inhibited the ethanol-induced increase in the tissue DA and DOPAC content in the ventral striatum. Similarly, pretreatment with cytisine (0.5 or 3 mg/kg) also reduced the ethanol-induced increase in the tissue DA and DOPAC content in the ventral striatum. However, when given alone lobeline or cytisine did not produce significant effect on the DA or DOPAC content in the ventral striatum compared with controls. These findings provide evidence that lobeline and cytisine modulate ethanol-induced DA function by targeting nicotinic acetylcholine receptors in the ventral striatum, a reward-relevant brain region implicated in ethanol dependence.