Tipepidine increases dopamine level in the nucleus accumbens without methamphetamine-like behavioral sensitization

•Acute administration of tipepidine increased dopamine levels in the nucleus accumbens.•Tipepidine did not cause behavioral sensitization in rats.•Cross-sensitization between tipepidine and methamphetamine was not observed in rats. We previously reported that the novel antidepressant-like effect of...

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Published in:	Behavioural brain research Vol. 284; pp. 118 - 124
Main Authors:	Hamao, Keiko, Kawaura, Kazuaki, Soeda, Fumio, Hamasaki, Ryota, Shirasaki, Tetsuya, Takahama, Kazuo
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 01-05-2015
Subjects:	Akathisia, Drug-Induced Animals Antidepressive Agents - pharmacology Antitussive Dopamine Dopamine - metabolism Dopamine Agents - pharmacology Dose-Response Relationship, Drug G protein-coupled inwardly rectifying potassium channel Male Methamphetamine - pharmacology Microdialysis Motor Activity - drug effects Nucleus accumbens Nucleus Accumbens - drug effects Nucleus Accumbens - metabolism Piperidines - pharmacology Rats, Sprague-Dawley Tipepidine Nucleus accumbens G protein-coupled inwardly rectifying potassium channel Dopamine Antitussive Tipepidine
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Summary:	•Acute administration of tipepidine increased dopamine levels in the nucleus accumbens.•Tipepidine did not cause behavioral sensitization in rats.•Cross-sensitization between tipepidine and methamphetamine was not observed in rats. We previously reported that the novel antidepressant-like effect of tipepidine may be produced at least partly through the activation of mesolimbic dopamine neurons via inhibition of G protein-coupled inwardly rectifying potassium channels. In this study, we investigated whether tipepidine increases dopamine levels in the nucleus accumbens (NAc) in rats using an in vivo microdialysis technique. We further assessed whether tipepidine at antidepressant-like effective doses induces behavioral- and cross-sensitization of locomotor activity in rats using the open field test. We found that acute administration of tipepidine increased dopamine levels in the NAc in freely moving rats without increasing locomotor activity. Tipepidine at antidepressant-like effective doses (20 and 40mg/kg, i.p.) did not cause behavioral sensitization in rats. Furthermore, cross-sensitization between tipepidine and methamphetamine was not observed in rats. These results further support our working hypothesis that tipepidine may produce a novel antidepressant-like effect through activation of ventral tegmental area-NAc dopaminergic neurons whose mechanisms differ from those contributing to the reinforcing effects of addictive drugs.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0166-4328 1872-7549
DOI:	10.1016/j.bbr.2015.02.012