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The antidepressant-like activity of nicotine, but not 3-furan-2-yl-N-p-tolyl-acrylamide, is regulated by the nicotinic receptor β4 subunit

Arias, HR and Targowska-Duda, KM and Feuerbach, Dominik and Jozwiak, K (2015) The antidepressant-like activity of nicotine, but not 3-furan-2-yl-N-p-tolyl-acrylamide, is regulated by the nicotinic receptor β4 subunit. Neuroscience letter.

Abstract

The current study compares the antidepressant-like effect elicited by nicotine between wild-type (4+/+) and knockout (beta4-/-) mice, and subsequently, the effect of 3-furan-2-yl-N-p-tolyl-acrylamide (PAM-2), a positive allosteric modulator of alpha7 nicotinic receptors (nAChRs), on the previously determined antidepressant-like activity of nicotine. Mice from each sex were injected daily with nicotine base (0.2 mg/kg; s.c.) alone or co-administered with PAM-2 (1.0 mg/kg; i.p.) for three weeks. Forced swim tests (FSTs) were performed to determine the acute (Day 1), subchronic (Day 7), and chronic (Days 14 and 21) effects of the drugs. To examine the residual effects after treatment cessation, FSTs were performed on Days 28 and 35. Our results indicate that nicotine (alone) mediates antidepressant-like activity after acute, subchronic, and chronic treatments in beta4+/+, but not beta4-/-, mice. However, nicotine+PAM-2 produces antidepressant-like activity in both beta 4+/+ and β4-/- mice, except after the acute treatment of β4-/- mice. This suggests that although the β4 subunit regulates the antidepressant-like activity of nicotine it does not affect the activity elicited by PAM-2 when is co-administered with nicotine. The residual antidepressant-like activity of nicotine+PAM-2 was observed only in female mice, suggesting gender-specific differences. Our findings clearly indicate that β4-containing nAChRs play an important role in the antidepressant-like activity elicited by nicotine but they are not essential for the modulatory activity of PAM-2. In fact, PAM-2 inhibits α4β4 AChRs at higher concentration range, in contrast with the PAM activity previously found at the α7 AChR.

Item Type: Article
Date Deposited: 26 Apr 2016 23:45
Last Modified: 26 Apr 2016 23:45
URI: https://oak.novartis.com/id/eprint/23840

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