A diencephalic circuit in rats for opioid analgesia but not positive reinforcement.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35140231.
- Also identified by DOI 10.1038/s41467-022-28332-6 and PMC identifier 8828762.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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.
Medical subject headings
- Analgesics, Opioid
- Receptors, Opioid, mu
- Reinforcement, Psychology