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Chlorpheniramine exerts anxiolytic-like effects and activates prefrontal 5-HT systems in mice.
- Source :
-
Psychopharmacology . Feb2011, Vol. 213 Issue 2/3, p441-452. 12p. - Publication Year :
- 2011
-
Abstract
- Rationale: The traditional antihistamine chlorpheniramine ameliorates panic attacks, phobias, and lowered mood, and this therapeutic effect is independent of the blockade of histamine H receptors. Since chlorpheniramine inhibits the reuptake of serotonin (5-HT), the anxiolytic-like effect of chlorpheniramine may be produced by an increase in serotonergic function. Objective: To elucidate the mechanisms underlying the anxiolytic-like effects of chlorpheniramine in mice, we examined the involvement of 5-HT systems in the prefrontal cortex that is a crucial region in the regulation of emotional function. Results: Chlorpheniramine (0.05-5 mg/kg, i.p.) dose-dependently and significantly decreased the duration of freezing behavior in both the elevated open-platform and conditioned fear tests. The anti-freezing effects of chlorpheniramine (5 mg/kg, i.p.) in these tests were inhibited by pretreatment with the non-selective antagonist at 5-HT receptors, methiothepin (0.01 mg/kg, s.c.). In addition, the local injection of chlorpheniramine (10-100 ng/mouse) and 5-HT (1-10 μg/mouse) into the medial part of the prefrontal cortex (mPFC) dose-dependently and significantly decreased the duration of freezing behavior in the elevated open-platform test. In a microdialysis study, chlorpheniramine (0.5 and 5 mg/kg, i.p.) dose-dependently and significantly increased the extracellular 5-HT level in the mPFC. In addition, the local perfusion of chlorpheniramine (10 and 30 μM), but not of the selective H1 receptor antagonist, cetirizine, into the mPFC markedly increased the extracellular 5-HT level in the mPFC. Conclusion: The anxiolytic-like effect of chlorpheniramine is produced, at least in part, by the facilitation of serotonergic neurotransmission in the PFC. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00333158
- Volume :
- 213
- Issue :
- 2/3
- Database :
- Academic Search Index
- Journal :
- Psychopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 57721784
- Full Text :
- https://doi.org/10.1007/s00213-009-1695-0