PMID- 37398335
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230902
IS  - 2692-8205 (Electronic)
IS  - 2692-8205 (Linking)
DP  - 2023 May 30
TI  - Alcohol inhibits sociability via serotonin inputs to the nucleus accumbens.
LID - 2023.05.29.542761 [pii]
LID - 10.1101/2023.05.29.542761 [doi]
AB  - Social interaction is a core component of motivational behavior that is perturbed 
      across multiple neuropsychiatric disorders, including alcohol use disorder (AUD). 
      Positive social bonds are neuroprotective and enhance recovery from stress, so 
      reduced social interaction in AUD may delay recovery and lead to alcohol relapse. 
      We report that chronic intermittent ethanol (CIE) induces social avoidance in a 
      sex-dependent manner and is associated with hyperactivity of serotonin (5-HT) 
      neurons in the dorsal raphe nucleus (DRN). While 5-HT (DRN) neurons are generally 
      thought to enhance social behavior, recent evidence suggests that specific 5-HT 
      pathways can be aversive. Using chemogenetic iDISCO, the nucleus accumbens (NAcc) 
      was identified as one of 5 regions that were activated by 5-HT (DRN) stimulation. 
      We then employed an array of molecular genetic tools in transgenic mice to show 
      that 5-HT (DRN) inputs to NAcc dynorphin neurons drive social avoidance in male 
      mice after CIE by activating 5-HT (2C) receptors. NAcc dynorphin neurons also 
      inhibit dopamine release during social interaction, reducing the motivational 
      drive to engage with social partners. This study reveals that excessive 
      serotonergic drive after chronic alcohol can promote social aversion by 
      inhibiting accumbal dopamine release. Drugs that boost brain serotonin levels may 
      be contraindicated for individuals with AUD.
FAU - Wang, Ruixiang
AU  - Wang R
AUID- ORCID: 0000-0003-0316-0600
FAU - Khan, Kanza M
AU  - Khan KM
AUID- ORCID: 0000-0003-4018-7669
FAU - Balasubramanian, Nagalakshmi
AU  - Balasubramanian N
AUID- ORCID: 0000-0001-6278-0231
FAU - James, Thomas
AU  - James T
FAU - Pushpavathi, Selvakumar Govindhasamy
AU  - Pushpavathi SG
FAU - Kim, David
AU  - Kim D
FAU - Pierson, Samantha
AU  - Pierson S
AUID- ORCID: 0000-0002-8376-4465
FAU - Wu, Qi
AU  - Wu Q
FAU - Niciu, Mark J
AU  - Niciu MJ
AUID- ORCID: 0000-0002-5612-3021
FAU - Hefti, Marco M
AU  - Hefti MM
AUID- ORCID: 0000-0002-3127-4528
FAU - Marcinkiewcz, Catherine A
AU  - Marcinkiewcz CA
AUID- ORCID: 0000-0001-7161-7815
LA  - eng
GR  - R00 AA024142/AA/NIAAA NIH HHS/United States
PT  - Preprint
DEP - 20230530
PL  - United States
TA  - bioRxiv
JT  - bioRxiv : the preprint server for biology
JID - 101680187
PMC - PMC10312479
EDAT- 2023/07/03 13:05
MHDA- 2023/07/03 13:06
PMCR- 2023/06/30
CRDT- 2023/07/03 11:45
PHST- 2023/07/03 13:06 [medline]
PHST- 2023/07/03 13:05 [pubmed]
PHST- 2023/07/03 11:45 [entrez]
PHST- 2023/06/30 00:00 [pmc-release]
AID - 2023.05.29.542761 [pii]
AID - 10.1101/2023.05.29.542761 [doi]
PST - epublish
SO  - bioRxiv [Preprint]. 2023 May 30:2023.05.29.542761. doi: 
      10.1101/2023.05.29.542761.