Additive effects of apomorphine and clonidine on serotonin neurons in the dorsal raphe |
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| Authors: | E H Lee |
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| Affiliation: | 1. Department of Pediatrics, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA;2. Department of Neurology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA;3. Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA;4. Department of Physiology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA;5. Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA;6. Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA;7. Department of Cardiology, Oklahoma University of Health Sciences Center, Oklahoma City, OK, USA;1. Department of Neurology, The First Affiliated Hospital of Xi''an Jiaotong University, Xi''an, 710061, China;2. Department of Neurology, The Affiliated Hospital of Jiujiang University, No.57 Xunyang East Rode, Xunyang District, Jiujiang, 332000, China;1. College of Pharmacy, Keimyung University, 1095 Dalgubeol-daero, Dalseo-Gu, Daegu 42601, Republic of Korea;2. Department of Biochemistry, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea;3. Department of Precision Medicine, School of Medicine, Sungkyunkwan University, Suwon 16419, Republic of Korea |
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| Abstract: | Effects of apomorphine (APO) and clonidine (CLON) on the mesostriatal and mesolimbic serotonergic systems were examined in the present study. Both drugs selectively elevated serotonin (5-HT) concentrations in the dorsal raphe and the striatum without significantly altering 5-HT measures in the median raphe and the hippocampus. Apomorphine also increased tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) levels in the dorsal raphe and 5-HIAA level in the striatum. Clonidine did not markedly alter tryptophan and 5-HIAA measures, while it decreased 5-HT turnover rate in both region, as indicated by the ratio of 5-HIAA/5-HT levels. Co-administration of APO and CLON, at doses of each drug exerted maximum effects on 5-HT alone, produced an additive effect on 5-HT in the dorsal raphe, while their effects on 5-HT and 5-HIAA in the striatum were counteracting each other. Effects of APO on 5-HT and 5-HIAA were attributed to the elevation of 5-HT precursor tryptophan, while effects of CLON on 5-HT and 5-HIAA were due to a decreased rate of 5-HT turnover. Therefore, the present results support the hypothesis that the additive effects of APO and CLON on dorsal raphe 5-HT are mediated through different receptors and neuropharmacological mechanisms. |
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