Neurons in the Locus Coeruleus Modulate the Hedonic Effects o

AAV-GCaMP6s was used for fiber photometry experiments. AAV-hM4D(Gi) was used for chemogenetic inhibition. (From BrainVTA)

The viruses used in this article from BrainVTA are in the table below

Calcium sensors	PT-0145 AVV-hSyn-GCaMP6s
Chemogenetics	PT-0153 rAAV-hSyn-hM4D(Gi)-EGFP

Hui Chen, Dan Xu, Yu Zhang, Yan Yan, JunXiao Liu, ChengXi Liu, Wei Shen, Tian Yu and Jin Liu
Pub Date: 2021-03-09, DOI: 10.3389/fnins.2021.636901, Email: [email protected]
Propofol is a worldwide-used intravenous general anesthetic with ideal effects, but hedonic effects of propofol have been reported and cause addictive issue. There is little known about the neurobiological mechanism of hedonic effects of propofol. Increasing researches have shown that the dopaminergic nervous system of the ventral tegmental area (VTA) and the noradrenergic system of locus coeruleus (LC) play a crucial role in hedonic experiences, which are putative sites for mediating the hedonic effects of propofol. In the present study, rat hedonic response scale and place conditioning paradigm were employed to examine the euphoric effects of propofol. In vivo GCaMP-based (AVV-hSyn-GCaMP6s) ﬁber photometry calcium imaging was used to monitor the real-time neuronal activity in VTA and LC area in rats exhibiting propofol-induced euphoric behaviors. Then DREADDs (designer receptors exclusively activated by designer drugs) modulation using rAAV-hSyn-hM4D(Gi)-EGFP was performed to conﬁrm the neuronal substrate that mediates the euphoric effects of propofol. The score of hedonic facial responses was signiﬁcantly increased in the 4 mg/kg group compared with that of the 0 mg/kg group. The locomotor activity in the propofol-paired compartment was signiﬁcantly increased at the 4 mg/kg dose compared with that of the saline-paired group. When compared with the 0 mg/kg group, the place preference increased in the 4 mg/kg group. Administration of 4 mg/kg of propofol triggers reliable increases in GcaMP ﬂuorescence. However, in the VTA GcaMP-expressing rats, administration of 4 mg/kg of propofol did not induce any change of GcaMP signals. The facial score and the place preference, which increased by 4 mg/kg propofol were abolished by chemogenetic inhibition of the neuronal activity in the LC area. Our results suggest that LC noradrenergic neurons, not VTA dopaminergic neurons, are directly involved in the hedonic effects of sub-anesthetic dose of propofol.

Figure 1. The hedonic effects of propofol (4 mg/kg, i.v.) are mediated by LC neurons.

The study is aimed to explore the neurobiological mechanism of hedonic effects of propofol. Using in vivo GCaMP6-based fiber photometry calcium imaging and DREADDs technology, the authors studied the role of the VTA neurons and LC neurons in the euphoric state induced by propofol. The results suggest that LC noradrenergic neurons, not VTA dopaminergic neurons, are directly involved in the hedonic effects of sub-anesthetic dose of propofol.

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