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LACK OF ANTIDEPRESSANT EFFECTS OF MECAMYLAMINE IN AN ANIMAL MODEL OF DEPRESSION
Author(s) -
Tizabi Yousef,
Hauser Sheketha
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a238
Subject(s) - mecamylamine , nicotine , nicotinic agonist , behavioural despair test , pharmacology , animal models of depression , antidepressant , tail suspension test , antagonist , nicotinic antagonist , endocrinology , medicine , receptor , hippocampus
Wistar‐Kyoto (WKY) rats are considered a suitable animal model of depression as they show exaggerated immobility in the forced swim test (FST) compared to their control the Wistar rats. Nicotine may act as an antidepressant or as an enhancer of the depressive characteristics of WKY rats depending on the testing paradigm. Thus, when the FST is carried out 16–18 hours after the last nicotine injection (7 day treatment), a reduction in the immobility is observed. However, if the test is carried out 15 min after the last nicotine dose there is an increase in immobility of WKY rats in the FST. It has been suggested that the antidepressant effects of nicotine may be due to desensitization or inactivation of the nicotinic receptors. To test this hypothesis, we evaluated the effects of chronic mecamylamine, a non‐competitive and non‐selective nicotinic receptor antagonist, alone or prior to nicotine administration in adult female WKY rats. Mecamylamine (0.1– 1.0 mg/kg, IP) administered once daily for 7 days did not have any effect on immobility of the WKY rats in the FST. However, daily administration of mecamylamine (0.8 mg/kg) prior to daily administration of nicotine (0.4 mg/kg) completely blocked the antidepressant effects of nicotine. These findings suggest that it is unlikely that the antidepressant effects of nicotine are due to desensitization or inactivation of central nicotinic receptors. Hence, selective nicotinic agonists may be of therapeutic potential in treatment of at least some depressive disorders. (Supported by NIH/NIGMS 2SO6 GM08016‐34)