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 |
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| Main Authors: | , , , , , |
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| Language: | English |
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| Abstract | •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. |
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| AbstractList | 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. 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. •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. |
| Author | Hamasaki, Ryota Shirasaki, Tetsuya Takahama, Kazuo Hamao, Keiko Soeda, Fumio Kawaura, Kazuaki |
| Author_xml | – sequence: 1 givenname: Keiko surname: Hamao fullname: Hamao, Keiko organization: Department of Environmental and Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan – sequence: 2 givenname: Kazuaki surname: Kawaura fullname: Kawaura, Kazuaki organization: Department of Environmental and Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan – sequence: 3 givenname: Fumio surname: Soeda fullname: Soeda, Fumio organization: Department of Environmental and Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan – sequence: 4 givenname: Ryota surname: Hamasaki fullname: Hamasaki, Ryota organization: Department of Environmental and Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan – sequence: 5 givenname: Tetsuya surname: Shirasaki fullname: Shirasaki, Tetsuya organization: Department of Environmental and Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan – sequence: 6 givenname: Kazuo surname: Takahama fullname: Takahama, Kazuo email: takahama@kumamoto-hsu.ac.jp organization: Department of Environmental and Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25687844$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_25259_IJPP_337_2022 crossref_primary_10_1016_j_tips_2020_12_002 crossref_primary_10_1016_j_neulet_2023_137245 crossref_primary_10_1016_j_bbr_2015_12_008 crossref_primary_10_1016_j_pbb_2016_02_006 crossref_primary_10_1111_pcn_13180 crossref_primary_10_1017_neu_2015_43 |
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| Keywords | Nucleus accumbens G protein-coupled inwardly rectifying potassium channel Dopamine Antitussive Tipepidine |
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| Snippet | •Acute administration of tipepidine increased dopamine levels in the nucleus accumbens.•Tipepidine did not cause behavioral sensitization in... We previously reported that the novel antidepressant-like effect of tipepidine may be produced at least partly through the activation of mesolimbic dopamine... |
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| SubjectTerms | 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 |
| Title | Tipepidine increases dopamine level in the nucleus accumbens without methamphetamine-like behavioral sensitization |
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