Serotonergic modulation of nicotine-induced kinetic tremor in mice.

Abstract

We previously demonstrated that nicotine elicited kinetic tremor by elevating the neural activity of the inferior olive via α7 nicotinic acetylcholine (nACh) receptors. Since α7 nACh receptors reportedly facilitate synaptic monoamine release, we explored the role of 5-HT receptors in induction and/or modulation of nicotine tremor. Treatment of mice with nicotine induced kinetic tremor that normally appeared during movement. The 5-HT1A agonist, 8-hydroxydipropylaminotetraline (8-OH-DPAT), significantly enhanced nicotine-induced tremor and the action of 8-OH-DPAT was antagonized by WAY-100135 (5-HT1A antagonist). In addition, the cerebral 5-HT depletion by repeated treatment with p-chlorophenylalanine did not reduce, but rather potentiated the facilitatory effects of 8-OH-DPAT. In contrast, the 5-HT2 agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI), significantly attenuated nicotine tremor, which was antagonized by ritanserin (5-HT2 antagonist). The 5-HT3 agonist SR-57227 did not affect nicotine-induced tremor. Furthermore, when testing the direct actions of 5-HT antagonists, nicotine tremor was inhibited by WAY-100135, but was unaffected by ritanserin, ondansetron (5-HT3 antagonist) or SB-258585 (5-HT6 antagonist). These results suggest that postsynaptic 5-HT1A receptors are involved in induction of nicotine tremor mediated by α7 nACh receptors. In addition, 5-HT2 receptors have an inhibitory modulatory role in induction of nicotine tremor.

• Authors: Naofumi Kunisawa, Higor A Iha, Yuji Nomura, Misaki Onishi, Nami Matsubara, Saki Shimizu, Yukihiro Ohno
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 134 Issue 2 Pg. 131-138 (Jun 2017) ISSN: 1347-8648 [Electronic] Japan
• PMID: 28647281 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Chemical References

• Amphetamines
• Piperazines
• Receptors, Serotonin
• Serotonin Antagonists
• Serotonin Receptor Agonists
• Receptor, Serotonin, 5-HT1A
• WAY 100135
• Ritanserin
• Ondansetron
• Nicotine
• 8-Hydroxy-2-(di-n-propylamino)tetralin
• 4-iodo-2,5-dimethoxyphenylisopropylamine
• Fenclonine

Topics

• 8-Hydroxy-2-(di-n-propylamino)tetralin (pharmacology, therapeutic use)
• Amphetamines (pharmacology)
• Animals
• Fenclonine (pharmacology)
• Humans
• Male
• Mice
• Nicotine (toxicity)
• Ondansetron (pharmacology)
• Piperazines (pharmacology)
• Receptor, Serotonin, 5-HT1A (metabolism)
• Receptors, Serotonin (metabolism)
• Ritanserin (pharmacology)
• Serotonin Antagonists (pharmacology)
• Serotonin Receptor Agonists (pharmacology, therapeutic use)
• Tremor (chemically induced, drug therapy, metabolism)