Central Processing of Itch in the Midbrain Reward Center.

Itch is an aversive sensation that evokes a desire to scratch. Paradoxically, scratching the itch also produces a hedonic experience. The specific brain circuits processing these different aspects of itch, however, remain elusive. Here, we report that GABAergic (GABA) and dopaminergic (DA) neurons in the ventral tegmental area (VTA) are activated with different temporal patterns during acute and chronic itch. DA neuron activation lags behind GABA neurons and is dependent on scratching of the itchy site. Optogenetic manipulations of VTA GABA neurons rapidly modulated scratching behaviors through encoding itch-associated aversion. In contrast, optogenetic manipulations of VTA DA neurons revealed their roles in sustaining recurrent scratching episodes through signaling scratching-induced reward. A similar dichotomy exists for the role of VTA in chronic itch. These findings advance understanding of circuit mechanisms of the unstoppable itch-scratch cycles and shed important insights into chronic itch therapy. • Itch elicits distinct activation patterns of GABA and DA neurons in VTA • GABA neurons signal aversion toward itch • DA neurons mediate reward to scratch-induced relief of itch • VTA neurons regulate scratching behaviors in chronic itch Su et al. demonstrate that VTA GABA neurons signal aversion to itch and DA neurons mediate scratching-associated reward. Differential activation and function of VTA neurons may underlie the progression of vicious itch-scratch cycles. [ABSTRACT FROM AUTHOR]