Tipepidine increases dopamine level in the nucleus accumbens without methamphetamine-like behavioral sensitization
| Autor: | Fumio Soeda, Kazuo Takahama, Ryota Hamasaki, Kazuaki Kawaura, Tetsuya Shirasaki, Keiko Hamao |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Microdialysis Dopamine Dopamine Agents Pharmacology Nucleus accumbens Motor Activity Open field Nucleus Accumbens Methamphetamine Rats Sprague-Dawley Behavioral Neuroscience Piperidines medicine Animals Dose-Response Relationship Drug Inward-rectifier potassium ion channel Chemistry Dopaminergic Antidepressive Agents Tipepidine medicine.drug Akathisia Drug-Induced |
| Zdroj: | Behavioural brain research. 284 |
| ISSN: | 1872-7549 |
| Popis: | 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 40 mg/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. |
| Databáze: | OpenAIRE |
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