Sex difference in dopamine D1-D2 receptor complex expression and signaling affects depression- and anxiety-like behaviors

Autor: Haneen Rahal, Rachel F. Tyndale, Ahmed Hasbi, Bertha K. Madras, Joshua D. Manduca, Tuan V. Nguyen, Melissa L. Perreault, Sharon Miksys, Susan R. George
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
medicine.medical_specialty
Receptor complex
Heteromer
lcsh:Medicine
Tropomyosin receptor kinase B
Anxiety
Nucleus accumbens
Biology
Nucleus Accumbens
lcsh:Physiology
Rats
Sprague-Dawley
Gender Studies
Glycogen Synthase Kinase 3
03 medical and health sciences
0302 clinical medicine
Endocrinology
Dopamine receptor D1
Dopamine
Internal medicine
Dopamine receptor D2
Chlorocebus aethiops
medicine
Animals
Receptor
trkB
beta Catenin
Sex Characteristics
Behavior
Animal
lcsh:QP1-981
Depression
Receptors
Dopamine D2
Brain-Derived Neurotrophic Factor
Receptors
Dopamine D1
Research
lcsh:R
030104 developmental biology
Female
2
3
4
5-Tetrahydro-7
8-dihydroxy-1-phenyl-1H-3-benzazepine
Caudate Nucleus
Proto-Oncogene Proteins c-akt
030217 neurology & neurosurgery
Signal Transduction
medicine.drug
Sex characteristics
Zdroj: Biology of Sex Differences, Vol 11, Iss 1, Pp 1-17 (2020)
Biology of Sex Differences
ISSN: 2042-6410
DOI: 10.1186/s13293-020-00285-9
Popis: Depression and anxiety are more common among females than males and represent a leading cause of disease-related disability in women. Since the dopamine D1-D2 heteromer is involved in depression- and anxiety-like behavior, the possibility that the receptor complex may have a role in mediating sex differences in such behaviors and related biochemical signaling was explored.In non-human primate caudate nucleus and in rat striatum, females expressed higher density of D1-D2 heteromer complexes and a greater number of D1-D2 expressing neurons compared to males. In rat, the sex difference in D1-D2 expression levels occurred even though D1 receptor expression was lower in female than in male with no difference in D2 receptor expression. In behavioral tests, female rats showed faster latency to depressive-like behavior and a greater susceptibility to the pro-depressive and anxiogenic-like effects of D1-D2 heteromer activation by low doses of SKF 83959, all of which were ameliorated by the selective heteromer disrupting peptide, TAT-D1. The sex difference observed in the anxiety test correlated with differences in low-frequency delta and theta oscillations in the nucleus accumbens. Analysis of signaling pathways revealed that the sex difference in D1-D2 heteromer expression led to differences in basal and heteromer-stimulated activities of two important signaling pathways, BDNF/TrkB and Akt/GSK3/β-catenin.These results suggest that the higher D1-D2 heteromer expression in female may significantly increase predisposition to depressive-like and anxiety-like behavior in female animals.
Databáze: OpenAIRE
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