Low frequency deep brain stimulation of nucleus accumbens shell neuronal subpopulations attenuates cocaine seeking selectively in male rats

Addiction neuroscience Pub Date : 2023-10-20 DOI:10.1016/j.addicn.2023.100133

Sarah E. Swinford-Jackson , Matthew T. Rich , Phillip J. Huffman , Melissa C. Knouse , Arthur S. Thomas , Sharvari Mankame , Samantha J. Worobey , R. Christopher Pierce

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Abstract

The present study examined the effect of deep brain stimulation (DBS) in the nucleus accumbens shell on cocaine seeking and neuronal plasticity in rats. Electrical DBS of the accumbens shell attenuated cocaine primed reinstatement across a range of frequencies as low as 12 Hz in male rats. Nucleus accumbens medium spiny neurons (MSNs) can be differentiated by expression of dopamine D1 receptors (D1DRs) or D2DRs. Low-frequency optogenetic-DBS in D1DR- or D2DR-containing neurons attenuated cocaine seeking in male but not female rats. In slice electrophysiology experiments, 12 Hz electrical stimulation evoked long term potentiation (LTP) in D1DR-MSNs and D2DR-MSNs from cocaine naive male and female rats. However, in cocaine-experienced rats, electrical and optical DBS only elicited LTP in D2DR-MSNs from male rats. These results suggest that low frequency DBS in the nucleus accumbens shell effectively, but sex-specifically, suppresses cocaine seeking, which may be associated with the reversal of synaptic plasticity deficits in D2DR-MSNs.

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低频脑深部刺激伏隔核壳神经元亚群选择性地减弱雄性大鼠的可卡因寻求

本研究检测了伏隔核壳脑深部刺激（DBS）对大鼠可卡因寻求和神经元可塑性的影响。伏隔壳的电DBS在低至12赫兹的频率范围内减弱了雄性大鼠可卡因引发的恢复。伏隔核中棘神经元（MSNs）可以通过多巴胺D1受体（D1DRs）或D2DRs的表达来分化。含有D1DR或D2DR的神经元中的低频光遗传学DBS减弱了雄性大鼠而非雌性大鼠的可卡因寻求。在切片电生理学实验中，12Hz电刺激在未摄入可卡因的雄性和雌性大鼠的D1DR MSN和D2DR MSN中诱发长时程增强（LTP）。然而，在经历可卡因的大鼠中，电和光DBS仅在雄性大鼠的D2DR MSNs中引发LTP。这些结果表明，伏隔核外壳中的低频DBS有效地抑制了可卡因寻求，但性别特异性抑制，这可能与D2DR MSNs突触可塑性缺陷的逆转有关。

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