3-Furan-2-yl-N-p-tolyl-acrylamide, a highly selective positive allosteric modulator of α7 nicotinic receptors, produces anxiolytic-like activity in mice
Autor: | Hugo R Arias, Barbara Budzyńska, Krzysztof Jozwiak, Katarzyna M. Targowska-Duda, Agnieszka Michalak, Grazyna Biala |
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Rok vydání: | 2019 |
Předmět: |
Male
Nicotine Allosteric modulator alpha7 Nicotinic Acetylcholine Receptor Anxiety Pharmacology Anxiolytic like Bridged Bicyclo Compounds Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Furan Animals Drug Interactions Pharmacology (medical) Nicotinic Agonists Furans 030304 developmental biology Acetylcholine receptor Acrylamides 0303 health sciences Behavior Animal Chemistry Highly selective Disease Models Animal Psychiatry and Mental health Nicotinic agonist α7 nicotinic receptor Acrylamide Benzamides 030217 neurology & neurosurgery |
Zdroj: | Journal of Psychopharmacology. 33:558-567 |
ISSN: | 1461-7285 0269-8811 |
Popis: | Background: Several lines of investigations support the idea that nicotinic acetylcholine receptors modulate neuronal pathways involved in anxiety and depression. Aims: The purpose of this study was to determine whether 3-furan-2-yl-N-p-tolyl-acrylamide, a highly selective positive allosteric modulator of α7 nicotinic acetylcholine receptors, influences anxiety-like behaviour in mice, and to determine the modulatory activity of 3-furan-2-yl-N-p-tolyl-acrylamide on mice pretreated with either nicotine or selective α7-agonists (i.e. PNU-282987 or (2.4)-dimethoxybenzylidene anabaseine dihydrochloride). Methods: The elevated plus maze and novelty suppressed feeding tests were selected to evaluate 3-furan-2-yl-N-p-tolyl-acrylamide and other nicotinic ligands on anxiety-like behaviour in mice. Results: The results indicated that: (a) 3-furan-2-yl-N-p-tolyl-acrylamide induces anxiolytic-like activity at 0.5 (elevated plus maze) and 1.0 (novelty suppressed feeding) mg/kg, respectively, after acute treatment, whereas its efficacy is increased after chronic treatments (i.e. active at 0.1 mg/kg; elevated plus maze). This is the first time showing anxiolytic-like activity elicited by 3-furan-2-yl-N-p-tolyl-acrylamide, contrary to the lack of activity for PNU-120596 (0.1 mg/kg); (b) the anxiolytic-like activity of 0.5 mg/kg 3-furan-2-yl-N-p-tolyl-acrylamide is inhibited by methyllycaconitine, a selective α7-antagonist, suggesting that α7 nicotinic acetylcholine receptors are involved in this process; (c) 0.5 mg/kg 3-furan-2-yl-N-p-tolyl-acrylamide reverses the anxiogenic effects induced by 0.1 mg/kg nicotine but not by 10.0 mg/kg PNU-282987; and (d) inactive doses of both 3-furan-2-yl-N-p-tolyl-acrylamide (0.1 mg/kg) and (2.4)-dimethoxybenzylidene anabaseine dihydrochloride (1.0 mg/kg) produce anxiolytic-like effects, suggesting drug interactions, probably synergistic. Conclusions: Our findings indicated that anxiolytic-like activity is mediated by α7 nicotinic acetylcholine receptors, supporting the concept that these receptors modulate anxiety processes. The results indicating that the chronic treatment with 3-furan-2-yl-N-p-tolyl-acrylamide is more efficient than the acute treatment in eliciting anxiolytic-like activity, and that 3-furan-2-yl-N-p-tolyl-acrylamide reverses the anxiogenic effects induced by nicotine, might be of therapeutic importance during smoking cessation. |
Databáze: | OpenAIRE |
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