title: Amphetamine augments action potential-dependent dopaminergic signaling in the striatum in vivo.
abstract: Amphetamine (AMPH) is thought to disrupt normal patterns of action potential-dependent dopaminergic signaling by depleting dopamine (DA) vesicular stores and promoting non-exocytotic DA efflux. Voltammetry in brain slices concurrently demonstrates these key drug effects, along with competitive inhibition of neuronal DA uptake. Here, we perform comparable kinetic and voltammetric analyses in vivo to determine whether AMPH acts qualitatively and quantitatively similar in the intact brain. Fast-scan cyclic voltammetry measured extracellular DA in dorsal and ventral striata of urethane-anesthetized rats. Electrically evoked recordings were analyzed to determine K(m) and V(max) for DA uptake and vesicular DA release, while background voltammetric current indexed basal DA concentration. AMPH (0.5, 3, and 10 mg/kg i.p.) robustly increased evoked DA responses in both striatal subregions. The predominant contributor to these elevated levels was competitive uptake inhibition, as exocytotic release was unchanged in the ventral striatum and only modestly decreased in the dorsal striatum. Increases in basal DA levels were not detected. These results are consistent with AMPH augmenting action potential-dependent dopaminergic signaling in vivo across a wide, behaviorally relevant dose range. Future work should be directed at possible causes for the distinct in vitro and in vivo pharmacology of AMPH.
authors: School of Biological Sciences, Illinois State University, Normal, Illinois 61790-4120, USA.
authors: Eric S
authors: ES
authors: Ramsson
authors: Daniel P
authors: DP
authors: Covey
authors: David P
authors: DP
authors: Daberkow
authors: Melissa T
authors: MT
authors: Litherland
authors: Steven A
authors: SA
authors: Juliano
authors: Paul A
authors: PA
authors: Garris
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D004558:Electric Stimulation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: D000697:Central Nervous System Stimulants; D000661:Amphetamine; D004298:Dopamine