Effects of metabolic alterations on dopamine release in an in vitro model of neostriatal ischaemia.
Release of neurotransmitters, including dopamine (DA), plays a central role in neuronal death during cerebral ischaemia. We investigated the effects of changes in energy demand and supply on DA release in cerebral ischaemia in vitro. Rat striatal slices were superfused (400 ml/h) with an artificial cerebrospinal fluid at 34 degrees C, unless otherwise stated. Ischaemia were mimicked by removal of O2 and reduction in glucose concentration from 4 to 2 mM. DA release was monitored by voltammetry. The profile of ischaemia-induced DA release was temperature-dependent. Hypothermia (to 24 degrees C) delayed, slowed, and reduced ischaemia-induced DA release relative to 34 degrees C. Pretreatment of the slices for 3 h with creatine (25 mM) delayed and slowed ischaemia-induced DA release. Conversely, blockade of Na+/K+ ATPase with ouabain induced an anoxic depolarisation and rapid DA release similar to ischaemia. In summary, the onset of DA release in this model is controlled by the balance between energy supply and utilisation. Strategies that increase availability of energy substrates for the membrane sodium pump (i.e., pre-incubation with creatine) or decrease their utilisation (hypothermia) slow and delay DA release. Hypothermia may owe part of its neuroprotective effect to a delay and slowing of ischaemia-induced release of DA and/or other neurotransmitters.
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Academic Department of Anaesthesia and Intensive Care, St. Bartholomew's and the Royal London School of Medicine and Dentistry, Royal London Hospital, Whitechapel, United Kingdom.
Stamford
J A
JA
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D003401:Creatine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004594:Electrophysiology; D000860:Hypoxia / Q000139:chemically induced / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D017072:Neostriatum / Q000098:blood supply* / Q000187:drug effects / Q000503:physiopathology; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013696:Temperature
D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D003401:Creatine; D004298:Dopamine