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Pentobarbital inhibits extracellular release of dopamine in the ischemic striatum

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Summary

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 extracellualr 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.

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References

  • Brannan T, Weinberger J, Knott P, Taff I, Kaufmann H, Togasaki D, Nieves-Rosa J, Maker H (1987) Direct evidence of acute, massive striatal dopamine release in gerbils with unilateral strokes. Stroke 18: 108–110

    Google Scholar 

  • Corkill G, Chikovani OK, McLeish I (1976) Timing of pentobarbital administration for brain protection in experimental stroke. Surg Neurol 5: 147–149

    Google Scholar 

  • Ginsberg MD, Graham DI, Busto R (1985) Regional glucose utilization and blood flow following graded forebrain ischemia in the rat: correlation with neuropathology. Ann Neurol 18: 470–481

    Google Scholar 

  • Globus MY-T, Busto R, Dietrich WD, Martinez E, Valdes I, Ginsberg MD (1988) Intraischemic extracellular release of dopamine and glutamate is associated with striatal vulnerability to ischemia. Neurosci Lett 91: 36–40

    Google Scholar 

  • Globus MY-T, Ginsberg MD, Dietrich WD, Busto R, Scheinberg P (1987) Substantia nigra lesion protects against ischemic damage in the striatum. Neurosci Lett 80: 251–256

    Google Scholar 

  • Gross RA, MacDonald RL (1988) Barbiturates and nifedipine have different and selective effects on calcium currents of mouse DRG neurons in cell culture: a possible basis for differing clinical actions. Neurology 38: 443–451

    Google Scholar 

  • Heyer EJ, McDonald RL (1982) Barbiturate reduction of calcium-dependent action potentials: correlation with anesthetic action. Brain Res 236: 157–171

    Google Scholar 

  • Ho IK, Harris RA (1981) Mechanism of action of barbiturates. Ann Rev Pharmacol Toxicol 21: 83–111

    Google Scholar 

  • Kahn K (1972) The natural course of experimental cerebral infarction in the gerbil. Neurology 22: 510–515

    Google Scholar 

  • Leslie SW, Friedman MB, Wilcox RE, Elrod SV (1980) Acute and chronic effects of barbiturates on depolarization-induced calcium influx into rat synaptosomes. Brain Res 185: 409–417

    Google Scholar 

  • Levine S, Payan H (1966) Effects of ischemia and other procedures on the brain and retina of the gerbil (meriones unguiculatus). Exp Neurol 16: 255–262

    Google Scholar 

  • Levy DE, Brierly JB (1979) Delayed pentobarbital administration limits ischemie brain damage in gerbils. Ann Neurol 5: 59–64

    Google Scholar 

  • Lightfoote WE II, Molinari GF, Chase TN (1977) Modification of cerebral ischemie damage by anesthetics. Stroke 8: 627–628

    Google Scholar 

  • Olsen RW (1982) Drug interactions at the GABA receptor-ionophore complex. Ann Rev Pharmacol Toxicol 22: 245–277

    Google Scholar 

  • Pulsinelli WA (1985) Selective neuronal vulnerability. Morphological and molecular characteristics. Prog Brain Res 63: 29–58

    Google Scholar 

  • Slivka A, Brannan TS, Weinberger J, Knott PJ, Cohen G (1988) Increase in extracellular dopamine in the striatum during cerebral ischemia: a study utilizing cerebral microdialysis. J Neurochem 50: 1714–1718

    Google Scholar 

  • Wages SH, Church WH, Justice Jr JB (1986) Sampling considerations for on-line microbore liquid chromatography of brain dialysates. Anal Chem 58: 1649–1656

    Google Scholar 

  • Weinberger J, Cohen G, Nieves-Rosa J (1983) Nerve terminal damage in cerebral ischemia: greater susceptibility of catecholamine nerve terminals relative to serotonin nerve terminals. Stroke 14: 986–989

    Google Scholar 

  • Weinberger J, Nieves-Rosa J, Cohen G (1985) Nerve terminal damage in cerebral ischemia: protective effect of alpha-methyl-para-tyrosine. Stroke 16: 864–870

    Google Scholar 

  • Weinberger J, Nieves-Rosa J (1987) Metabolism of monoamine neurotransmitters in the evolution of infarction in ischemic striatum. J Neural Transm 69: 265–275

    Google Scholar 

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Bhardwaj, A., Brannan, T. & Weinberger, J. Pentobarbital inhibits extracellular release of dopamine in the ischemic striatum. J. Neural Transmission 82, 111–117 (1990). https://doi.org/10.1007/BF01245167

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  • DOI: https://doi.org/10.1007/BF01245167

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