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Neurobehavioral and molecular changes in a rodent model of ACTH-induced HPA axis dysfunction
Farhanah N Sallie1, Leandrie Pienaar1, Andrea Lubbe1
1Wits Integrated Molecular Physiology Research Initiative, Wits Health Consortium (PTY) Ltd, School of Physiology, Faculty of Health Sciences, University of The Witwatersrand, Johannesburg, South Africa; School of Physiology, Faculty of Health Sciences, University of The Witwatersrand, Johannesburg, South Africa.
Adrenocorticotropic hormone (ACTH) induced depressive-like behaviors and altered neurotrophic factors in male rats, but not females. Imipramine failed to reverse these ACTH-induced changes, suggesting sex-specific mechanisms in HPA axis dysregulation.
Area of Science:
- Neuroscience
- Endocrinology
- Psychiatry
Background:
- Hypothalamic-pituitary-adrenal (HPA) axis dysregulation is implicated in depression.
- Exogenous adrenocorticotropic hormone (ACTH) administration in rodents is linked to depressive-like phenotypes, but requires further neurobehavioral and mechanistic validation.
Purpose of the Study:
- To investigate the neurobehavioral and molecular effects of ACTH administration in a rodent model.
- To explore the potential therapeutic effects of imipramine on ACTH-induced changes.
- To determine sex-specific responses to ACTH administration and its impact on HPA axis dysregulation.
Main Methods:
- Sprague-Dawley rats (male and female) received daily subcutaneous ACTH (100 μg/day) or saline for two weeks.
- Subsequent treatment involved ACTH with either saline or imipramine (10 mg/kg) for four weeks.
- Neurobehavioral assessments included the forced swim test (FST), sucrose preference test (SPT), and open field test (OFT).
- Brain regional mRNA expression of BDNF and CREB was analyzed using RT-PCR.
Main Results:
- ACTH administration significantly increased immobility in the FST, decreased center interaction in the OFT, and increased sucrose consumption in male rats, but not females.
- ACTH elevated hippocampal BDNF and whole-brain CREB expression in males.
- Imipramine treatment did not ameliorate the observed ACTH-induced behavioral or molecular alterations.
Conclusions:
- ACTH administration induces sex-specific depressive-like symptoms and neurotrophic factor alterations in rats.
- These findings highlight sex-specific mechanisms in the development of depressive-like behavior associated with HPA axis dysregulation.
- The results suggest that imipramine may not be effective in reversing ACTH-induced depressive-like phenotypes.
