Spinal pathways involved in somatosensory inhibition of the psychomotor actions of cocaine

Previous studies have demonstrated that somatosensory stimuli influence dopamine transmission in the mesolimbic reward system and can reduce drug-induced motor behaviors, craving and dependence. Until now, the central links between somatosensory and brain reward systems are not known. Here, we show that the dorsal column (DC) somatosensory pathway contains projections that convey an inhibitory input from the periphery to mesolimbic reward circuits. Stimulation of the ulnar nerve under HT7 acupoint suppressed psychomotor response to cocaine, which was abolished by disruption of the DC pathway, but not the spinothalamic tract (STT). Low-threshold or wide-dynamic range neurons in the cuneate nucleus (CN) were excited by peripheral stimulation. Lesions of dorsal column or lateral habenula (LHb) prevented the inhibitory effects of peripheral stimulation on cocaine-induced neuronal activation in the nucleus accumbens (NAc). LHb neurons projecting to the ventral tegmental area (VTA)/rostromedial tegmental nucleus (RMTg) regions were activated by peripheral stimulation and LHb lesions reversed the inhibitory effects on cocaine locomotion produced by peripheral stimulation. These findings suggest that there exists a pathway in spinal cord that ascends from periphery to mesolimbic reward circuits (spino-mesolimbic pathway) and the activation of somatosensory input transmitted via the DC pathway can inhibit the psychomotor response to cocaine.