British journal of pharmacology · 2026
The medial prefrontal cortex-ventral tegmental area dopaminergic circuit regulates the pleasure of tactile contact by releasing dopamine in the nucleus accumbens.
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Zhai Jinhe, Xu Zihan, Yu Xinran, Shi Keqing, Zhang Xiaoyan, Kuniishi Hiroshi, Xie Min Jue, Zhang Yuying, Yao Xueke, Wang Xinxin, Cao Xuan, Zhang Xinyi, Li Dongxin, Zhang Jie, Xu Yi, Fan Lili, Wu Lijie, Wang Jia
Аннотация
BACKGROUND AND PURPOSE: Tactile contact during social interactions is believed to enhance the experience of pleasure. Dopaminergic neurons in the ventral tegmental area (VTA) are crucial for the regulation of pleasurable emotions. We aim to reveal the specific circuit mechanisms by which the VTA contributes to pleasure derived from tactile contact.
EXPERIMENTAL APPROACH: Paradigms of social interaction in the presence of physical contact (SIPPC) and social interaction in the absence of physical contact (SIAPC) were established. The expression of c-fos in different brain regions was detected by immunofluorescence. A combination of behavioural tests, fibre-optic calcium imaging, chemogenetics, patch-clamp techniques and molecular biological methods were used to investigate the circuit mechanism mediating pleasure of tactile contact.
KEY RESULTS: Dopaminergic neurons in the VTA were implicated in triggering pleasurable emotions associated with SIPPC. Mechanistically, SIPPC promoted the disinhibition of presynaptic neurons and enhanced excitatory synaptic transmission. Furthermore, projections from the mPFC to VTA dopaminergic neurons were activated during SIPPC. Chemogenetic activation of the mPFC-VTADA circuit increased SIPPC-induced pleasure, whereas its inhibition decreased it. SIPPC triggered dopamine release in the nucleus accumbens (NAc), where the inhibition of dopamine receptors (D1R) can reverse the pleasure-promoting effect of mPFC-VTADA circuit activation during SIPPC.
CONCLUSIONS AND IMPLICATIONS: Collectively, these findings elucidate the key roles and mechanisms by which VTADA neurons receive projections from the mPFC and subsequently release dopamine in the NAc to regulate the pleasure induced by tactile contact, which provide new insights into the mechanisms underlying the association between tactile and social interaction.
EXPERIMENTAL APPROACH: Paradigms of social interaction in the presence of physical contact (SIPPC) and social interaction in the absence of physical contact (SIAPC) were established. The expression of c-fos in different brain regions was detected by immunofluorescence. A combination of behavioural tests, fibre-optic calcium imaging, chemogenetics, patch-clamp techniques and molecular biological methods were used to investigate the circuit mechanism mediating pleasure of tactile contact.
KEY RESULTS: Dopaminergic neurons in the VTA were implicated in triggering pleasurable emotions associated with SIPPC. Mechanistically, SIPPC promoted the disinhibition of presynaptic neurons and enhanced excitatory synaptic transmission. Furthermore, projections from the mPFC to VTA dopaminergic neurons were activated during SIPPC. Chemogenetic activation of the mPFC-VTADA circuit increased SIPPC-induced pleasure, whereas its inhibition decreased it. SIPPC triggered dopamine release in the nucleus accumbens (NAc), where the inhibition of dopamine receptors (D1R) can reverse the pleasure-promoting effect of mPFC-VTADA circuit activation during SIPPC.
CONCLUSIONS AND IMPLICATIONS: Collectively, these findings elucidate the key roles and mechanisms by which VTADA neurons receive projections from the mPFC and subsequently release dopamine in the NAc to regulate the pleasure induced by tactile contact, which provide new insights into the mechanisms underlying the association between tactile and social interaction.