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Chemogenetic inhibition of lateral habenula projections to the dorsal raphe nucleus reduces passive coping and perseverative reward seeking in rats
- Source :
- Neuropsychopharmacology
- Publication Year :
- 2020
- Publisher :
- Springer International Publishing, 2020.
-
Abstract
- The lateral habenula (LHb) processes information about aversive experiences that contributes to the symptoms of stress disorders. Previously, we found that chemogenetic inhibition of rat LHb neurons reduced immobility in the forced swim test, but the downstream target of these neurons was not known. Using an intersectional viral vector strategy, we selectively transduced three different output pathways from the LHb by injecting AAV8-DIO-hM(4)Di into the LHb and CAV2-CRE (a retrograde viral vector) into one of the three target areas as follows: dorsal raphe nucleus (DRN), ventral tegmental area (VTA), or rostromedial tegmentum (RMTg). Using the forced swim test, we found that chemogenetic inhibition of DRN-projecting LHb neurons reduced passive coping (immobility), whereas inhibition of the other pathways did not. Chemogenetic activation of DRN-projecting neurons using hM3Dq in another cohort did not further exacerbate immobility. We next examined the impact of inhibiting DRN-projecting LHb neurons on reward sensitivity, perseverative behavior, and anxiety-like behavior using saccharin preference testing, reward-omission testing, and open-field testing, respectively. There was no effect of inhibiting any of these pathways on reward sensitivity, locomotion, or anxiety-like behavior, but inhibiting DRN-projecting LHb neurons reduced perseverative licking during reward-omission testing, whereas activating these neurons increased perseverative licking. These results support the idea that inhibiting LHb projections to the DRN provides animals with resilience during highly stressful or frustrating conditions but not under low-stress circumstances, and that inhibiting these neurons may promote persistence in active coping strategies.
- Subjects :
- Dorsal Raphe Nucleus
Male
endocrine system
Tegmentum Mesencephali
Genetic Vectors
Passive coping
Biology
Transfection
Article
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Dorsal raphe nucleus
Reward
Adaptation, Psychological
Neural Pathways
Tegmentum
medicine
Animals
Saccharin
Clozapine
Lateral habenula
Pharmacology
Habenula
Immobility Response, Tonic
Neural Inhibition
030227 psychiatry
Rats
Ventral tegmental area
Psychiatry and Mental health
medicine.anatomical_structure
chemistry
Licking
Neuroscience
030217 neurology & neurosurgery
hormones, hormone substitutes, and hormone antagonists
Locomotion
Behavioural despair test
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Neuropsychopharmacology
- Accession number :
- edsair.doi.dedup.....21e6199f72c5f4126b7364b57e0ffd4d