Amantadine enhances nigrostriatal and mesolimbic dopamine function in the rat brain in relation to motor and exploratory activity
| Autor: | Joseph P. Huston, Maria A. de Souza Silva, Christina Antke, Anja Müller-Lutz, Markus Beu, Hans-Jörg Wittsack, Hans-Wilhelm Müller, Hubertus Hautzel, Susanne Nikolaus, Frithjof Wickrath, Gerald Antoch |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
medicine.medical_specialty Dopamine Clinical Biochemistry Medizin Hippocampus Motor Activity Nucleus accumbens Toxicology Biochemistry Open field Receptors Dopamine 03 medical and health sciences Behavioral Neuroscience 0302 clinical medicine Internal medicine Dopamine receptor D2 Amantadine Limbic System medicine Radioligand Animals Rats Wistar Biological Psychiatry Pharmacology business.industry Dopaminergic Corpus Striatum Rats 030227 psychiatry Substantia Nigra Endocrinology Exploratory Behavior business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Pharmacology Biochemistry and Behavior. 179:156-170 |
| ISSN: | 0091-3057 |
| DOI: | 10.1016/j.pbb.2018.12.010 |
| Popis: | Purpose The present study assessed the influence of the NMDA receptor (R) antagonist amantadine (AMA) on cerebral dopamine D2/3R binding in relation to motor and exploratory activity in the rat. Methods D2/3R binding was determined in anaesthetized animals with small animal SPECT in baseline and after challenge with AMA (10 or 40 mg/kg) using [123I]IBZM as radioligand. Immediately post-challenge and prior to radioligand administration, motor/exploratory behaviors were assessed for 30 min in an open field. Each rat underwent measurements with a dedicated small animal MRI in order to gain anatomical information. Regions of interest were defined on SPECT-MRI overlays. The regional binding potentials in baseline and post-challenge were estimated by computing ratios of the specifically bound compartments to the cerebellar reference region. Results 40 mg/kg AMA reduced D2/3R binding in nucleus accumbens, caudateputamen and thalamus, while 10 mg/kg decreased D2/3R binding in the anterodorsal hippocampus. The higher dose decreased ambulatory activity, rearing and grooming, but elevated sitting and head-shoulder motility relative to both vehicle and the lower dose in the first 15 min post-challenge. Conclusions Results showed reductions of D2/3R binding in regions of the nigrostriatal and mesolimbic system after challenge with AMA, which reflect an increased availability of dopamine. Thereby, an inverse relationship between nigrostriatal and mesolimbic dopamine and motor/exploratory activity can be inferred. Findings may be relevant for the treatment of neurological and psychiatric conditions such as Parkinson's disease, Huntington's disease or schizophrenia, which are characterized by both dopaminergic and glutamatergic dysfunction. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect