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Hyperactivity of hypothalamic pituitary axis in neonatal clomipramine model of depression
J Prathiba1, K B Kumar, K S Karanth
1Department of Pharmacology, Kasturba Medical College, Manipal, Karnataka, India.
Insights
Neonatal clomipramine treatment in rats caused hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, indicated by elevated corticosterone. REM sleep deprivation normalized these HPA axis responses in the depression model.
Area of Science:
- Neuroscience
- Endocrinology
- Pharmacology
Background:
- The hypothalamic-pituitary-adrenal (HPA) axis is crucial for stress response.
- Depression is often associated with HPA axis dysregulation.
- Clomipramine is a widely used antidepressant medication.
Purpose of the Study:
- To investigate the long-term effects of neonatal clomipramine exposure on HPA axis function.
- To determine if REM sleep deprivation can modulate HPA axis activity in this model.
Main Methods:
- Neonatal rats were treated with clomipramine during a critical developmental period.
- HPA axis integrity was assessed in adulthood by measuring corticosterone levels.
- Tests included baseline levels, dexamethasone suppression, and response to REM sleep deprivation.
Main Results:
- Clomipramine-treated rats exhibited heightened baseline corticosterone levels.
- These rats showed a lack of corticosterone suppression following dexamethasone administration.
- REM sleep deprivation reversed the HPA axis hyperactivity to control levels.
Conclusions:
- Neonatal clomipramine exposure induces lasting HPA axis hyperactivity in rats.
- This hyperactivity is linked to cholinergic system changes in the depression model.
- REM sleep deprivation offers a potential therapeutic avenue for normalizing HPA axis function in depression.
Abstract:
This study examined the integrity of hypothalamic-pituitary-adrenal (HPA) axis in clomipramine model of depression. Male rat pups were treated twice daily from postnatal day 5 to 21 with clomipramine (15 mg/kg, s.c.). At three months of age, serum corticosterone level was estimated before and after dexamethasone (100 microg/kg, s.c.) administration and after subjected to REM sleep deprivation (RSD) for 4 days consecutively. Data indicated enhanced baseline corticosterone levels and nonsuppression to dexamethasone in clomipramine treated rats. The corticosterone levels however, reversed to the levels of control group in rats subjected to RSD. These findings thus indicated for the first time an HPA hyperactivity in rats treated with clomipramine during neonatal period and are in harmony with cholinergic hypersensitivity reported earlier in this model of depression.