'Real time' measurement of dopamine release in an in vitro model of neostriatal ischaemia.
Dopamine (DA) is released in large quantities during ischaemia and may be neurotoxic. For instance, reduction of DA release is associated with a better histological outcome following experimental stroke. In the present study, we report the measurement of transmitter release in an in vitro model of cerebral ischaemia using brain slices. Striatal slices were subjected to 'ischaemia' by reducing the O2 and glucose content of the superfusate in a controlled fashion. The resultant monoamine release, measured in real time by fast cyclic voltammetry at carbon fibre microelectrodes, was shown to be DA by electrochemical criteria. Upon imposition of an ischaemic episode, there was a lag period (159 +/- 2 s, mean +/- S.E.M., n = 99) followed by a sudden release of DA, reaching a maximum extracellular concentration of 95 +/- 4 microM in 25 +/- 2 s. This overall profile of DA release was qualitatively similar to that measured in the striatum in vivo following cardiac arrest. The DA uptake inhibitor GBR 12935 (1.0 microM) had no effect on any DA release variable. We conclude that this model mimics many of the features of cerebral ischaemia in vivo and may be a suitable vehicle for the investigation of neuroprotective drugs.
Toner
C C
CC
Anaesthetics Unit (Neurotransmission Laboratory), London Hospital Medical College, Whitechapel, UK.
Stamford
J A
JA
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D002545:Brain Ischemia / Q000378:metabolism*; D003199:Computer Systems; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004594:Electrophysiology / Q000295:instrumentation / Q000379:methods*; D005947:Glucose / Q000378:metabolism; D006324:Heart Arrest, Induced; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D010477:Perfusion; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D018765:Dopamine Uptake Inhibitors; D008024:Ligands; D010879:Piperazines; C044630:1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine; D005947:Glucose; D004298:Dopamine