The Role of Dopaminergic VTA Neurons in General Anesthesia

Zhou, Xi‐Lang; Yin, Wei Hsian; Zhang, Chenjing; Wang, Min; Zhang, Mei; Lu, Yu; Yan, Min

doi:10.1371/journal.pone.0138187

Cited by 33 publications

(30 citation statements)

References 23 publications

(33 reference statements)

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“…We hypothesized that the regulation of the ventral reticular activation system after NB injury was impaired, which weakened the nerve projection of NB to a certain extent, and thus reduced the activity of FC neurons, i.e., the increase in the proportion of low-frequency high-delta band. The damage to the ventral tegmental dopaminergic neurons significantly increased propofol recovery time but did not change propofol sensitivity and induction time [22]. Just like our results, the sensitivity and induction time of propofol were not affected after NB injury, indicating that anesthesia recovery is not a reverse process of anesthesia induction.…”

supporting

confidence: 72%

Propofol Causes Consciousness Loss by Affecting GABA-A Receptor in the Nucleus Basalis of Rats

Xing

Yuan

et al. 2020

Behavioural Neurology

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Objective. Propofol is a classical anesthetic and induces consciousness loss, and gamma-aminobutyric-acid-type-A (GABA-A) receptor is its target. Righting reflex is associated with conscious response. The nucleus basalis (NB) acts as a major relay between the reticular activating system and the frontal cortex (FC). Propofol may mediate righting reflex by affecting GABA-A receptor in NB. Methods. Fifty male SD rats (250-350 g) were divided into parts I and II. In part I, 20 male SD rats were randomly divided into control group (CG) and NB-lesion group (NG, ibotenic acid-induced NB lesion). In part II, 30 male SD rats were treated with saline (0.9% NaCl, SG group), muscimol (a GABA-A receptor agonist, MG group), and gabazine (a GABA-A receptor antagonist, GG group) in NB, respectively. Two weeks later, the activity of the rats was measured between CG and NG groups. The rats were intravenously injected with propofol (50 mg/kg/h) to test the time of loss of righting reflex (LORR) in all rats. When LORR occurred, the rats received single administration of propofol (12 mg/kg) to measure the time of return of righting reflex (RORR). Electroencephalogram (EEG) activity of the frontal cortex (FC) was recorded. Results. The numbers of NB neurons were reduced by 44% in the NG group compared to the CG group (p<0.05) whereas the activity of rats was reduced a little in the NG group when compared with the CG group, but the statistical difference was insignificant (p>0.05). The dose-response curve of propofol shifted to the left in the NG group, and the statistical difference for the time of LORR was insignificant between the two groups (p>0.05). However, the time of RORR and FC delta power increased in the NG group compared with the CG group (p<0.05). In part II, the time of RORR and FC powder increased in the MG group when compared to the SG group while reverse results were observed in the GG group (p<0.05). There was no significant influence on the time of LORR and ED50 among the three groups (p>0.05). Conclusions. The unilateral NB lesion increased the recovery time and FC delta power, and the NB region might be involved in the emergence after propofol administration. Propofol plays a crucial role for causing conscious loss by affecting GABA-A receptor in NB.

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supporting

confidence: 72%

Propofol Causes Consciousness Loss by Affecting GABA-A Receptor in the Nucleus Basalis of Rats

Xing

Yuan

et al. 2020

Behavioural Neurology

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“…A variety of experimental approaches have been used to study the neural circuits that underlie anesthetic-induced unconsciousness and recovery of consciousness in rodents, including designer receptors exclusively activated by designer drugs (DREADDs) (35), genetic manipulations (36), local and systemic drug administration (10,(37)(38)(39), microdialysis (40,41), targeted brain lesions (42,43), and electrical stimulation (34). Optogenetics is a novel tool that provides distinct advantages over previous techniques used to study anesthetic-induced unconsciousness and recovery of consciousness in rodents.…”

Section: Discussionmentioning

confidence: 99%

Optogenetic activation of dopamine neurons in the ventral tegmental area induces reanimation from general anesthesia

Taylor

Dort

Kenny

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

211

179

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Dopamine (DA) promotes wakefulness, and DA transporter inhibitors such as dextroamphetamine and methylphenidate are effective for increasing arousal and inducing reanimation, or active emergence from general anesthesia. DA neurons in the ventral tegmental area (VTA) are involved in reward processing, motivation, emotion, reinforcement, and cognition, but their role in regulating wakefulness is less clear. The current study was performed to test the hypothesis that selective optogenetic activation of VTA DA neurons is sufficient to induce arousal from an unconscious, anesthetized state. Floxed-inverse (FLEX)-Channelrhodopsin2 (ChR2) expression was targeted to VTA DA neurons in DA transporter (DAT)-cre mice (ChR2+ group; n = 6). Optical VTA stimulation in ChR2+ mice during continuous, steady-state general anesthesia (CSSGA) with isoflurane produced behavioral and EEG evidence of arousal and restored the righting reflex in 6/6 mice. Pretreatment with the D1 receptor antagonist SCH-23390 before optical VTA stimulation inhibited the arousal responses and restoration of righting in 6/6 ChR2+ mice. In control DAT-cre mice, the VTA was targeted with a viral vector lacking the ChR2 gene (ChR2− group; n = 5). VTA optical stimulation in ChR2− mice did not restore righting or produce EEG changes during isoflurane CSSGA in 5/5 mice. These results provide compelling evidence that selective stimulation of VTA DA neurons is sufficient to induce the transition from an anesthetized, unconscious state to an awake state, suggesting critical involvement in behavioral arousal.anesthesia | ventral tegmental area | dopamine | optogenetics | arousal

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“…One study in California mice found no effect of social defeat stress on D1 receptors in the only area examined, the NAcc (Campi, Greenberg, Kapoor, Ziegler, & Trainor, ). Dopamine neurons, and specifically D1 receptors (Taylor, Chemali, Brown, & Solt, ), are involved in the arousal from anesthesia (Zhou et al, ); and chronic stress can cause a reduction in dopamine transmission (Mizoguchi et al, ). It is thus theoretically possible that reduced dopamine transmission caused by the stress of anesthesia could result in an up‐regulation of D1 neurons.…”

Section: Discussionmentioning

confidence: 99%

Effects of pair bonding on dopamine D1 receptors in monogamous male titi monkeys (Callicebus cupreus)

Hostetler

Hinde

Maninger³

et al. 2016

American J Primatol

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Pair bonding leads to increases in dopamine D1 receptor (D1R) binding in the nucleus accumbens of monogamous prairie voles. In the current study, we hypothesized that there is similar upregulation of D1R in a monogamous primate, the titi monkey (Callicebus cupreus). Receptor binding of the D1R antagonist [11C]-SCH23390 was measured in male titi monkeys using PET scans before and after pairing with a female. We found that within-subject analyses of pairing show significant increases in D1R binding in the lateral septum, but not the nucleus accumbens, caudate, putamen, or ventral pallidum. The lateral septum is involved in a number of processes that may contribute to social behavior, including motivation, affect, reward, and reinforcement. This region also plays a role in pair bonding and paternal behavior in voles. Our observations of changes in D1R in the lateral septum, but not the nucleus accumbens, suggest that there may be broadly similar dopaminergic mechanisms underlying pair bonding across mammalian species, but that the specific changes to neural circuitry differ. This study is the first research to demonstrate neuroplasticity of the dopamine system following pair bonding in a non-human primate; however, substantial variability in the response to pairing suggests the utility of further research on the topic.

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The Role of Dopaminergic VTA Neurons in General Anesthesia

Cited by 33 publications

References 23 publications

Propofol Causes Consciousness Loss by Affecting GABA-A Receptor in the Nucleus Basalis of Rats

Propofol Causes Consciousness Loss by Affecting GABA-A Receptor in the Nucleus Basalis of Rats

Optogenetic activation of dopamine neurons in the ventral tegmental area induces reanimation from general anesthesia

Effects of pair bonding on dopamine D1 receptors in monogamous male titi monkeys (Callicebus cupreus)

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