title: Distinct pharmacological regulation of evoked dopamine efflux in the amygdala and striatum of the rat in vivo.
abstract: The pharmacological regulation of evoked extracellular dopamine was compared in the basolateral amygdaloid nucleus (BAN) and caudate-putamen (CP) of the urethane-anesthetized rat. The effects of drugs, which alter dopamine uptake, release or degradation, were examined. Dopamine efflux was elicited by electrical stimulation of ascending dopamine fibers and was monitored by fast-scan cyclic voltammetry at Nafion-coated, carbon-fiber microelectrodes. Dopamine uptake inhibitors, nomifensine (25 mg/kg) and cocaine (20 mg/kg), and the dopamine receptor antagonist, haloperidol (0.5 mg/kg), robustly increased evoked extracellular dopamine in the CP. In sharp contrast, these drugs were much less effective in the BAN. The relative potencies of the uptake inhibitors varied between the two regions. Nomifensine was more potent than cocaine in the CP, whereas cocaine was more potent that nomifensine in the BAN. The monoamine oxidase inhibitor, pargyline (75 mg/kg), and the catechol-O-methyltransferase (COMT) inhibitor, Ro 40-7592 (40 mg/kg), had small or negligible effects in either region. No electrochemical evidence was found for the formation of 3-methoxytyramine, the dopamine metabolite formed by the action of COMT on released dopamine, on the time scale of the measurements in control or after pharmacological manipulation of the degradative enzymes for dopamine. The conclusions reached are: (1) potent mechanisms for uptake and autoreceptor inhibition of release, which exist in the CP to tightly control the concentration of extracellular dopamine, are considerably weaker in the BAN; (2) the extracellular clearance of evoked dopamine in the BAN and CP is the result of cellular uptake and not degradation; and (3) these results support the view that the pharmacological regulation of extracellular dopamine is regionally distinct in the brain.
authors.affiliation: Department of Chemistry, University of North Carolina, Chapel Hill 27599-2390, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Garris
authors.forename: R M
authors.initials: RM
authors.lastname: Wightman
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004558:Electric Stimulation; D004563:Electrochemistry; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008839:Microelectrodes; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009627:Nomifensine / Q000494:pharmacology; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D009627:Nomifensine; D003042:Cocaine; D004298:Dopamine