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

Suchan Chang,Chae Ha Yang,Young Seob Gwak,Eun Young Jang,Jun Yeon Lee,Jin Mook Kim,Yeonhee Ryu,Seol Ah Kim,Nam Jun Kim,Bong Hyo Lee,Scott C Steffensen,Hee Young Kim

doi:10.1038/s41598-017-05681-7

Abstract

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.

Highlights

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
To identify the ascending spinal pathway contributing to peripheral stimulation-induced inhibition of drug-induced behaviors, we hypothesized that: 1) Selective lesions of the dorsal column (DC) or spinothalamic tract (STT) pathways would affect sensory stimulation-induced inhibition of cocaine locomotor activity; 2) DC nuclei would be activated by specific peripheral stimulation; 3) Surgical transection of the DC or STT pathways would decrease the inhibition of cocaine modulation of the nucleus accumbens (NAc) by peripheral stimulation; 4) Peripheral stimulation would activate the lateral habenula (LHb); and 5) LHb lesions would disrupt sensory stimulation-induced effects on cocaine locomotion or neuronal activation in NAc
Mechanical stimulation of the ulnar site after sectioning the ulnar nerve had no effect on cocaine-induced locomotion (Fig. 1B; p > 0.05), suggesting that somatosensory-induced inhibition of cocaine-induced locomotion was mediated through activation of the ulnar nerve

Summary

Introduction

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. 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. To identify the ascending spinal pathway contributing to peripheral stimulation-induced inhibition of drug-induced behaviors, we hypothesized that: 1) Selective lesions of the DC or STT pathways would affect sensory stimulation-induced inhibition of cocaine locomotor activity; 2) DC nuclei would be activated by specific peripheral stimulation; 3) Surgical transection of the DC or STT pathways would decrease the inhibition of cocaine modulation of the NAc by peripheral stimulation; 4) Peripheral stimulation would activate the lateral habenula (LHb); and 5) LHb lesions would disrupt sensory stimulation-induced effects on cocaine locomotion or neuronal activation in NAc

Methods

Results

Conclusion