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Published on: October 24, 2018
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Social isolation stress and neuroactive steroids
M Serra1, E Sanna, M C Mostallino
1Department of Experimental Biology, Center of Excellence for Neurobiology of Dependence, University of Cagliari, Cagliari 09100, Italy. mserra@unica.it
Summary
Social isolation in rats alters brain chemistry, increasing stress response and ethanol
Area of Science:
- Neuroscience
- Endocrinology
- Behavioral Science
Background:
- Social isolation post-weaning in rats reduces progesterone and its metabolites.
- While basal adrenocorticotropic hormone levels are slightly decreased, the steroidogenic machinery remains largely unchanged.
- The hypothalamic-pituitary-adrenal (HPA) axis shows a heightened response to stress and certain drug challenges in isolated rats.
Purpose of the Study:
- To investigate the neurobiological and behavioral effects of social isolation in rats.
- To explore the impact of isolation on the HPA axis, steroidogenesis, and GABAergic signaling.
- To determine the role of 5alpha-reductase in mediating the effects of isolation and ethanol.
Main Methods:
- Measurement of plasma hormone concentrations (progesterone, metabolites, ACTH).
- Assessment of steroidogenic machinery components (peripheral benzodiazepine receptors, StAR).
- Functional testing of the HPA axis response to stress and drugs (ethanol, isoniazid).
- Behavioral assays for ethanol's effect on isoniazid-induced convulsions.
- Analysis of StAR mRNA and protein levels, GABA(A) receptor subunit expression (alpha4, delta).
- Electrophysiological recordings of GABA(A) receptor-mediated currents (tonic and miniature).
Main Results:
- Social isolation reduces progesterone and its metabolites but increases HPA axis reactivity.
- Ethanol's anticonvulsant effect is enhanced in isolated rats, an effect reversed by finasteride.
- Isolation alters ethanol's effects on brain StAR, suggesting mitochondrial cholesterol transport changes.
- Increased alpha4 and delta GABA(A) receptor subunits in the hippocampus lead to enhanced tonic inhibition.
- Ethanol potentiates GABA(A) receptor-mediated synaptic currents in isolated rats, inhibited by finasteride.
Conclusions:
- Social isolation profoundly impacts neuroendocrine and neurochemical systems in rats.
- Enhanced GABAergic inhibition and HPA axis sensitivity are key consequences of isolation.
- The 5alpha-reductase pathway plays a crucial role in modulating ethanol's effects and the neurobiological adaptations to social isolation.
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