title: Methamphetamine neurotoxicity decreases phasic, but not tonic, dopaminergic signaling in the rat striatum.
abstract: Neurotoxic doses of methamphetamine (METH) are known to cause depletions in striatal dopamine (DA) tissue content. However, the effects of METH-induced insults on dopaminergic neurotransmission are not fully understood. Here, we employed fast-scan cyclic voltammetry at a carbon-fiber microelectrode in the anesthetized rat striatum to assess the effects of a neurotoxic regimen of METH on phasic and tonic modes of dopaminergic signaling and underlying mechanisms of DA release and uptake. Extracellular DA was electrically evoked by stimulation of the medial forebrain bundle mimicking tonic and phasic firing patterns for dopaminergic cells and was monitored simultaneously in both the dorsomedial and dorsolateral striatum. Kinetic analysis of evoked recordings determined parameters describing DA release and uptake. Striatal DA tissue content was quantified by high performance liquid chromatography with electrochemical detection. METH-pretreatment (four doses of 7.5 or 10.0 mg/kg s.c.) induced DA depletions of ∼ 40% on average, which are reported in both striatal subregions. METH pre-treatment significantly decreased the amplitude of signals evoked by phasic, but not tonic, stimulation. Parameters for DA release and uptake were also similarly reduced by ∼ 40%, consistent with effects on evoked phasic-like responses and DA tissue content. Taken together, these results suggest that METH-pretreatment selectively diminishes phasic, but not tonic, dopaminergic signaling in the dorsal striatum.
authors.affiliation: Cell Biology, Physiology and Development Section, School of Biological Sciences, Illinois State University, Normal, Illinois 61790-4120, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Howard
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Keefe
authors.forename: Paul A
authors.initials: PA
authors.lastname: Garris
authors.forename: David P
authors.initials: DP
authors.lastname: Daberkow
mesh_terms: D000465:Algorithms; D000818:Animals; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D003342:Corpus Striatum / Q000503:physiopathology*; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D004558:Electric Stimulation; D055724:Electrophysiological Phenomena; D005110:Extracellular Space / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D008839:Microelectrodes; D009474:Neurons / Q000502:physiology; D020258:Neurotoxicity Syndromes / Q000503:physiopathology*; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D013563:Sympathectomy, Chemical; D013565:Sympatholytics
chemical_list: D000697:Central Nervous System Stimulants; D013565:Sympatholytics; D008694:Methamphetamine; D016627:Oxidopamine; D004298:Dopamine