RRC ID 6351
著者 Donohoe DR, Jarvis RA, Weeks K, Aamodt EJ, Dwyer DS.
タイトル Behavioral adaptation in C. elegans produced by antipsychotic drugs requires serotonin and is associated with calcium signaling and calcineurin inhibition.
ジャーナル Neurosci Res
Abstract Chronic administration of antipsychotic drugs produces adaptive responses at the cellular and molecular levels that may be responsible for both the main therapeutic effects and rebound psychosis, which is often observed upon discontinuation of these drugs. Here we show that some antipsychotic drugs produce significant functional changes in serotonergic neurons that directly impact feeding behavior in the model organism, Caenorhabditis elegans. In particular, antipsychotic drugs acutely suppress pharyngeal pumping, which is regulated by serotonin from the NSM neurons. By contrast, withdrawal from food and drug is accompanied by a striking recovery and overshoot in the rate of pharyngeal pumping. This rebound response is absent or diminished in mutant strains that lack tryptophan hydroxylase (TPH-1) or the serotonin receptors SER-7 and SER-1, and is blocked by serotonin antagonists, which implicates serotonergic mechanisms in this adaptive response. Consistent with this, continuous drug exposure stimulates an increase in serotonin and the number of varicosities along the NSM processes. Cyclosporin A and calcineurin mutant strains mimic the effects of the antipsychotic drugs and reveal a potential role for the calmodulin-calcineurin signaling pathway in the response of serotonergic neurons. Similar molecular and cellular changes may contribute to the long-term adaptive response to antipsychotic drugs in patients.
巻・号 64(3)
ページ 280-9
公開日 2009-7-1
DOI 10.1016/j.neures.2009.03.012
PII S0168-0102(09)00092-3
PMID 19447297
PMC PMC2692945
MeSH Adaptation, Physiological / drug effects* Animals Antipsychotic Agents / administration & dosage* Caenorhabditis elegans* / drug effects Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins Calcineurin Inhibitors* Calcium Signaling* Cyclosporine / pharmacology Enzyme Inhibitors / pharmacology Feeding Behavior / drug effects Humans Imidazoles / pharmacology Methiothepin / pharmacology Neurons / drug effects Neurons / metabolism Psychotic Disorders / drug therapy Psychotic Disorders / metabolism Receptors, Serotonin / deficiency Receptors, Serotonin, 5-HT2 / deficiency Serotonin / metabolism* Serotonin Antagonists / pharmacology Tryptophan Hydroxylase / metabolism
IF 2.645
引用数 16
WOS 分野 NEUROSCIENCES
リソース情報
線虫 tm1325