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Brain stimulation rewarding experience attenuates neonatal clomipramine-induced adulthood anxiety by reversal of pathological changes in the amygdala.

Abstract：

:Major depressive disorder (MDD) is associated with enhanced anxiety and reduced reward processing leading to impaired cognitive flexibility. These pathological changes during depression are accompanied by dysfunctional hypothalamic-pituitary-adrenal (HPA) axis and its impaired regulation by the amygdala. Notably, the electrical stimulation of brain reward areas produces an antidepressant effect in both MDD patients and animal models of depression. However, the effects of chronic electrical self-stimulation of lateral hypothalamus - medial forebrain bundle (LH-MFB) on depression-associated anxiety and accompanying changes in plasma corticosterone levels, structural, and neurochemical alterations in the amygdala are unknown. Here, we used the neonatal clomipramine (CLI) model of depression. During adulthood, neonatal CLI and vehicle administered rats were subjected to bilateral electrode implantation at LH-MFB and trained to receive intracranial self-stimulation (ICSS) for 14 days. Rats were then tested for anhedonic and anxiety-like behaviors, followed by estimation of plasma corticosterone levels, assessment of amygdalar volumes and neuronal/glial numbers, levels of monoamines and their metabolites in the amygdala. We found that chronic ICSS of LH-MFB reverses CLI-induced anhedonia and anxiety. Interestingly, amelioration of CLI-induced enhanced anhedonia and anxiety in ICSS rats was associated with partial reversal of enhanced plasma corticosterone levels, hypertrophy of basolateral amygdala (BLA), and altered noradrenaline (NA) metabolism in the amygdalar complex. We suggest that beneficial effects of ICSS on CLI-induced anxiety at least in part mediated by the restoration of amygdalar and HPA axis functioning. Our results support the hypothesis that brain stimulation rewarding experience might be evolved as a therapeutic strategy for reversal of amygdalar dysfunction in depression.

journal_name

Prog Neuropsychopharmacol Biol Psychiatry

journal_title

Progress in neuro-psychopharmacology & biological psychiatry

authors

Chakraborty S,Tripathi SJ,Raju TR,Shankaranarayana Rao BS

doi

10.1016/j.pnpbp.2020.110000

subject

Has Abstract

pub_date

2020-12-20 00:00:00

pages

110000

eissn

0278-5846

issn

1878-4216

pii

S0278-5846(20)30316-X

journal_volume

103

pub_type

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Brain stimulation rewarding experience attenuates neonatal clomipramine-induced adulthood anxiety by reversal of pathological changes in the amygdala.