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Effects of neonatal clomipramine on cholinergic receptor sensitivity and passive avoidance behavior in adult rats
J Prathiba1, K B Kumar, K S Karanth
1Department of Pharmacology, Kasturba Medical College, Karnataka, India.
Insights
Neonatal clomipramine treatment in rats enhanced cholinergic system activity, leading to increased hypothermia and improved passive avoidance behavior. This suggests long-term changes in central cholinergic system sensitivity.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- The central cholinergic system plays a crucial role in regulating various cognitive and physiological functions.
- Altered cholinergic activity is implicated in several neurological and psychiatric disorders, including depression.
- Neonatal exposure to certain compounds can have lasting effects on neurodevelopment and system sensitivity.
Purpose of the Study:
- To investigate the long-term effects of neonatal clomipramine administration on the central cholinergic system.
- To assess changes in cholinergic receptor sensitivity and passive avoidance behavior in adult rats exposed to clomipramine during early development.
Main Methods:
- Rat pups received daily subcutaneous injections of clomipramine (15 mg/kg) from postnatal day 5 to 21.
- At 3 months of age, animals were challenged with oxotremorine to measure thermic responses (hypothermia).
- Passive avoidance learning and memory retention were assessed 24 hours after training.
Main Results:
- Clomipramine-treated rats exhibited significantly enhanced cholinomimetic-induced hypothermia, indicating increased cholinergic sensitivity.
- These animals also demonstrated improved performance in the passive avoidance test, with increased latency.
- The findings suggest a lasting alteration in the central cholinergic system's sensitivity.
Conclusions:
- Neonatal clomipramine treatment can lead to persistent changes in central cholinergic system function in rats.
- The observed enhancements in cholinergic sensitivity and passive avoidance behavior may provide insights into animal models of depression.
- Further research is warranted to explore the therapeutic potential and underlying mechanisms of these effects.
Abstract:
The effects of neonatal treatment with clomipramine on the sensitivity of cholinergic receptor and passive avoidance behavior were studied to examine the activity of the central cholinergic system. Rat pups were treated twice daily from postnatal day 5 to 21 with clomipramine (15 mg/kg, s.c.) and at 3 months of age the thermic responses to three different doses of oxotremorine were measured. One day following oxotremorine challenge study, the animals were subjected to passive avoidance training and retention was measured 24-hr later. Clomipramine treated animals showed an enhanced cholinomimetic-induced hypothermia and an increased latency in passive avoidance test. These findings may reflect an altered sensitivity of central cholinergic system in rats given clomipramine as neonates. The results were compared to other animal models of depression.
