Role of the nicotinic receptor β4 subunit in the antidepressant activity of novel N,6-dimethyltricyclo[5.2.1.02,6]decan-2-amine enantiomers

Katarzyna M. Targowska-Duda, Krzysztof Jozwiak, Hugo R. Arias

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

The role of the nicotinic receptor β4 subunit in the antidepressant activity of N,6-dimethyltricyclo[5.2.1.02,6]decan-2-amine enantiomers was investigated using wild-type (β4+/+) and knockout (β4-/-) mice. Mice were injected (i.p.) with saline (control) or with either enantiomer (1.0mg/kg base drug) daily for the first two weeks. Forced swim tests (FST) were performed on Day 1 to determine the acute effect of each enantiomer, and on Day 7 and 14, to determine the chronic activity. To examine the remnant effects after drug treatment, a withdrawal period of two more weeks was continued with FSTs performed on Day 21 and 28. Our results indicate that: (1) the acute antidepressant effect elicited by the (S,S)-enantiomer is observed in β4+/+ mice from both sexes, whereas the effect elicited by the (R,R)-enantiomer is only observed in male β4+/+ mice. There is no antidepressant effect for both novel compounds on male and female β4-/- mice, (2) the chronic antidepressant effect elicited by both enantiomers is observed in β4+/+, but not in β4-/-, mice from both sexes, and (3) the residual antidepressant effect mediated by each enantiomer after withdrawal was observed only in female β4+/+ mice. Our results clearly indicate that β4-containing AChRs are targets for the antidepressant activity of these compounds, and that this activity is gender-dependent.

Original languageEnglish
Pages (from-to)186-190
Number of pages5
JournalNeuroscience Letters
Volume553
DOIs
StatePublished - 11 Oct 2013
Externally publishedYes

Keywords

  • β4 Subunit
  • Antidepressants
  • Forced swim test
  • Knock-out mice
  • Nicotinic acetylcholine receptors

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