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Ventral tegmental area (VTA) and substantia nigra pars compacta (SNpc) are midbrain structures known to be involved in mediating reward in rodents.Lateral habenula (LHb) is considered as a negative reward source and it is reported that stimulation of the LHb rapidly induces inhibition of firing in midbrain dopamine neurons.Interestingly, the phasic fall in LHb neuronal activity may follow the excitation of dopamine neurons in response to reward-predicting stimuli.The VTA and SNpc give rise to dopaminergic projections that innervate the LHb, which is also known to be involved in processing painful stimuli.But its unclear what physiological effects these inputs have on habenular function.In this study we distinguished the LHb pain-activated neurons of the Wistar rats and assessed their electrophysiological responsiveness to the stimulation of the VTA and SNpc with either single-pulse stimulation (300 mA, 0.5 Hz) or tetanic stimulation (80 mA, 25 Hz).Single-pulse stimulation that was delivered to either midbrain structure triggered transient inhibition of firing of 90% of the LHb painactivated neurons.However, tetanic stimulation of the VTA tended to evoke an elevation in neuronal firing rate.We conclude that LHb pain-activated neurons can receive diverse reward-related signals originating from midbrain dopaminergic structures, and thus participate in the regulation of the brain reward system via both positive and negative feedback mechanisms.