title: Time window of autoreceptor-mediated inhibition of limbic and striatal dopamine release.
abstract: Forebrain dopamine release is under the local control of D2 family (D2 and D3) autoreceptors. In this study, autoreceptor-mediated modulation of forebrain dopamine release was investigated using amperometry in brain slices following local electrical stimulation. 350 microm-thick slices of nucleus accumbens or dorsolateral neostriatum were prepared from male Wistar rats (150-200 g) and superfused with artificial cerebrospinal fluid at 32 degrees C. Dopamine release was evoked by electrical pulses (0.1 ms, 10 mA) across bipolar tungsten stimulating electrodes and measured at carbon fibre microelectrodes using fixed potential amperometry (+300 mV vs. Ag/AgCl). Peak dopamine release on stimulation (single pulse) was 0.75 microM (neostriatum) and 1.37 microM (nucleus accumbens). Metoclopramide (1 microM) had no significant effect on DA efflux from a single pulse in either region. Using paired pulse stimuli, dopamine release on the second pulse varied according to the interval between the two pulses. At very long intervals (>20 sec), dopamine release was similar to that for the first pulse. At shorter intervals, dopamine efflux was attenuated. Metoclopramide had no effect on second pulse dopamine release when the pulse was applied at short (<0.1 sec) or long (>5.0 sec) intervals after the first. At intermediate intervals, metoclopramide significantly increased second pulse dopamine release. The peak dopamine autoreceptor effect occurred at approximately 550 ms in neostriatum and approximately 700 ms in nucleus accumbens. The onset time is due both to diffusion of dopamine from the release sites to the autoreceptors and receptor-effector mechanisms. These findings may have implications for the local control of forebrain dopamine function in physiological and pathological states.
authors.affiliation: Neurotransmission Laboratory, Academic Department of Anaesthesia and Intensive Care, Barts and The London School of Medicine and Dentistry, Alexandra Wing, Royal London Hospital, Whitechapel, London E1 1BB, UK.
authors.forename: Paul E M
authors.initials: PE
authors.lastname: Phillips
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Hancock
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Stamford
mesh_terms: D000818:Animals; D017660:Autoreceptors / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004558:Electric Stimulation; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism
chemical_list: D017660:Autoreceptors; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D008787:Metoclopramide; D004298:Dopamine