Pentobarbital inhibits extracellular release of dopamine in the ischemic striatum.
We examined whether pentobarbital (PB) inhibited the acute extracellular release of dopamine that occurs in the striatum following the onset of ischemic injury in the gerbil model of stroke. The cerebral dialysis technique was employed to monitor striatal extracellular dopamine concentrations before and after carotid artery occlusion while perfusing either a control solution of artificial cerebrospinal fluid (CSF) or a 1 mM solution of pentobarbital in CSF (PB/CSF). During perfusion with CSF, extracellular dopamine increased from a baseline concentration of 0.40 +/- 0.09 (SEM) pmoles/10 minute collection interval to 30.0 +/- 9.0 pmoles/10 minutes after carotid artery occlusion. In contrast, during perfusion with PB/CSF, dopamine levels increased from a baseline of 1.37 +/- 0.3 pmoles/10 minutes to 8.30 +/- 2.6 pmoles/10 minutes; this increase was significantly less than the increase in controls. In animals with established ischemia, repeatedly alternating the perfusion fluid between CSF and PB/CSF demonstrated that dopamine concentrations were significantly increased with CSF alone and decreased with PB/CSF. These findings demonstrate that pentobarbital perfusion either before or following the onset of ischemia inhibits extracellular release of dopamine in the striatum. Inhibition of neurotransmitter release may, in part, be responsible for the protective effect of pentobarbital in ischemic brain injury.
Bhardwaj
A
A
Department of Neurology, Mount Sinai School of Medicine, New York, NY.
Brannan
T
T
Weinberger
J
J
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003864:Depression, Chemical; D004298:Dopamine / Q000378:metabolism*; D005110:Extracellular Space / Q000737:chemistry; D005849:Gerbillinae; D006719:Homovanillic Acid / Q000032:analysis; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology*; D012636:Secretory Rate / Q000187:drug effects
D015102:3,4-Dihydroxyphenylacetic Acid; D010424:Pentobarbital; D004298:Dopamine; D006719:Homovanillic Acid