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Midbrain dopamine neurons are implicated in various psychiatric and neurological disorders. The GABAergic tail of the ventral tegmental area (tVTA), also named the rostromedial tegmental nucleus (RMTg), displays dense projections to the midbrain and exerts electrophysiological control over dopamine cells of the VTA. However, the influence of the tVTA on the nigrostriatal pathway, from the substantia nigra pars compacta (SNc) to the dorsal striatum, and on related functions remains to be addressed. The present study highlights the role played by the tVTA as a GABA brake for the nigrostriatal system, demonstrating a critical influence over motor functions. Using neuroanatomical approaches with tract tracing and electron microscopy, we reveal the presence of a tVTA-SNc-dorsal striatum pathway. Using in vivo electrophysiology, we prove that the tVTA is a major inhibitory control center for SNc dopamine cells. Using behavioral approaches, we demonstrate that the tVTA controls rotation behavior, motor coordination, and motor skill learning. The motor enhancements observed after ablation of the tVTA are in this regard comparable with the performance-enhancing properties of amphetamine, a drug used in doping. These findings demonstrate that the tVTA is a major GABA brake for nigral dopamine systems and nigrostriatal functions, and they raise important questions about how the tVTA is integrated within the basal ganglia circuitry. They also warrant further research on the tVTA's role in motor and dopamine-related pathological contexts such as Parkinson's disease.

DP is able to prevent alcohol-relapse-like drinking in rats suggesting that this drug may be a useful new tool in the management of relapse in alcohol-dependent patients.

The posterior VTA is another brain region involved in the locomotor activation after the intracerebroventricular administration of ethanol or acetaldehyde. Our data indicate that opioid receptors, particularly the micro-opioid receptors, could be the target of the actions of these compounds in the VTA. These results are consistent with the hypothesis that acetaldehyde could be a mediator of some ethanol effects.

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Salsolinol induces locomotor activity and motor sensitization after intra-VTA administration. Moreover, the implication of the mu-opioid receptors was shown since the treatment with naltrexone or beta-FNA was able to suppress the salsolinol effects.

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