L-cysteine prevents acetaldehyde and ethanol-induced increase in dopaminergic neuronal activity in the VTA

New evidence shows that acetaldehyde (ACD), the main metabolite of alcohol, may be involved in the neurochemical basis of the reinforcing effects of ethanol (EtOH). In fact, ACD is readily self-administered and stimulates the firing of Ventral Tegmental Area (VTA) mesolimbic dopaminergic neurons by an action on Ia and Ih. Further, D-penicillamine (DP) a selective ACD- sequestering agent reduces spontaneous ethanol drinking and ethanol-induced place preference. To further investigate the role of ACD on the dopamine stimulating properties of EtOH, we studied the effects of ACD and EtOH on VTA dopaminergic cells using single unit extracellular recordings coupled with antidromic identification from the Nucleus Accumbens (NAcb) in rats pre-treated with L-cysteine (L- cyst), a thiol aminoacid with ACD-sequestering properties. Administration of ACD (5-20 mg/kg i.v.) dose-dependently increased the firing rate, spikes/burst and burst firing of VTA neurons. EtOH (250-1000 mg/kg) administration produced similar effects in the same electrophysiological parameters. On the contrary, in animals preteated with L-cyst (50 mg/kg intraperitoneal, 30’ before drug challenge) EtOH and ACD effects on neuronal activity , were drastically reduced. These data support the idea that EtOH increases in vivo neuronal activity of Nacb-projecting VTA dopaminergic neurons via ACD. Furthermore, our result suggest that ACD plays a key role in the EtOH stimulation of mesolimbic pathway and contributes to the centrally positive motivational properties of EtOH.