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Mesolimbic circuits modulate reward (Biol Psychiatry 2006; 59:1151), and deep brain stimulation of the nucleus accumbens (NAc) has shown preliminary evidence of efficacy in treatment-resistant depression (Neuropsychopharmacology 2012; 37:1975). These data support the hypothesis that dopaminergic neurons in the ventral tegmental area (VTA) are involved in depressive behaviors. To test this, investigators used optogenetic methods (JW Psychiatry Jul 12 2010) to modify VTA dopamine neurons in mice so that light excited or inhibited firing of the neurons.
In one experiment, inhibiting VTA dopamine neurons produced depression-like behaviors in three paradigms that are established methods of testing for antidepressant drug efficacy in humans — the …