Distinct dose‐dependent effects of methamphetamine on real‐time dopamine transmission in the rat nucleus accumbens and behaviors
| Autor: | Caroline E. Bass, Megan Vik, Caitlin Szalkowski, Jinwoo Park, Ken T. Wakabayashi, Rohan V. Bhimani |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Dopamine Fast-scan cyclic voltammetry Motor Activity Pharmacology Nucleus accumbens Synaptic Transmission Biochemistry Article Nucleus Accumbens Methamphetamine Rats Sprague-Dawley Cellular and Molecular Neuroscience chemistry.chemical_compound Dopamine Uptake Inhibitors medicine Extracellular Animals Behavior Animal Dose-Response Relationship Drug Receptors Dopamine D2 Chemistry Meth Rats Systemic administration Autoreceptor Central Nervous System Stimulants Neurotoxicity Syndromes Stereotyped Behavior medicine.drug |
| Zdroj: | J Neurochem |
| ISSN: | 1471-4159 0022-3042 |
| DOI: | 10.1111/jnc.15470 |
| Popis: | Methamphetamine (METH) is a potent psychostimulant that exerts many of its physiological and psychomotor effects by increasing extracellular dopamine (DA) concentrations in limbic brain regions. While several studies have focused on how potent, neurotoxic doses of METH augment or attenuate DA transmission, the acute effects of lower and behaviorally-activating doses of METH on modulating DA regulation (release and clearance) through DA D2 autoreceptors and transporters remains to be elucidated. In this study, we investigated how systemic administration of escalating, sub-neurotoxic doses of METH (0.5 – 5 mg/kg, IP) alter extracellular DA regulation in the nucleus accumbens (NAc), in both anesthetized and awake-behaving rats through the use of in vivo fast-scan cyclic voltammetry. Pharmacological, electrochemical, and behavioral evidence show that lower doses (≤ 2.0 mg/kg, IP) of METH enhance extracellular phasic DA concentrations and locomotion as well as stereotypies. In contrast, higher doses (≥ 5.0 mg/kg) further increase both phasic and baseline DA concentrations and stereotypies but decrease horizontal locomotion. Importantly, our results suggest that acute METH-induced enhancement of extracellular DA concentrations dose-dependently activate D2 autoreceptors. Therefore, these different METH dose-dependent effects on mesolimbic DA transmission may distinctly impact METH induced behavioral changes. This study provides valuable insights regarding how low METH doses alter DA transmission and paves the way for future clinical studies on the reinforcing effects of METH. |
| Databáze: | OpenAIRE |
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