A diencephalic circuit in rats for opioid analgesia but not positive reinforcement.

Autor: Waung MW; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Maanum KA; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Cirino TJ; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Driscoll JR; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., O'Brien C; Department of Psychology, Rutgers University, New Brunswick, NJ, USA., Bryant S; Department of Psychology, Rutgers University, New Brunswick, NJ, USA., Mansourian KA; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Morales M; National Institute on Drug Abuse, Neuronal Networks Section, National Institutes of Health, Baltimore, MD, USA., Barker DJ; Department of Psychology, Rutgers University, New Brunswick, NJ, USA.; National Institute on Drug Abuse, Neuronal Networks Section, National Institutes of Health, Baltimore, MD, USA., Margolis EB; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA. Elyssa.Margolis@ucsf.edu.; Neuroscience Graduate Program, University of California, San Francisco, CA, USA. Elyssa.Margolis@ucsf.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Feb 09; Vol. 13 (1), pp. 764. Date of Electronic Publication: 2022 Feb 09.
DOI: 10.1038/s41467-022-28332-6
Abstrakt: Mu opioid receptor (MOR) agonists are potent analgesics, but also cause sedation, respiratory depression, and addiction risk. The epithalamic lateral habenula (LHb) signals aversive states including pain, and here we found that it is a potent site for MOR-agonist analgesia-like responses in rats. Importantly, LHb MOR activation is not reinforcing in the absence of noxious input. The LHb receives excitatory inputs from multiple sites including the ventral tegmental area, lateral hypothalamus, entopeduncular nucleus, and the lateral preoptic area of the hypothalamus (LPO). Here we report that LHb-projecting glutamatergic LPO neurons are excited by noxious stimulation and are preferentially inhibited by MOR selective agonists. Critically, optogenetic stimulation of LHb-projecting LPO neurons produces an aversive state that is relieved by LHb MOR activation, and optogenetic inhibition of LHb-projecting LPO neurons relieves the aversiveness of ongoing pain.
(© 2022. The Author(s).)
Databáze: MEDLINE
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