Ischemia-induced extracellular release of serotonin plays a role in ca1 neuronal cell death in rats

Mordecai Y.T. Globus, Per Wester, Raul Busto, W. Dalton Dietrich

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


Background and Purpose: Serotonin, via 5-HT2 receptors, exerts an excitatory effect on CA1 neurons and may play a role in ischemia-induced excitotoxic damage. To evaluate the role of serotonin in ischemia, both neurochemical and histopathological studies were performed. Methods: Neurochemical studies included rats that were subjected to 12.5 or 20 minutes of normothermic ischemia by two-vessel occlusion plus hypotension, and extracellular serotonin levels were measured in the hippocampus (12.5 minutes' ischemia, n=5) or striatum (20 minutes' ischemia, n = 13) by microdialysis. In the histopathological study the effect of 8 nig/kg ritanserin, a 5-HT2 antagonist, administered continuously from 30 minutes prior to ischemia until 1 hour of recirculation was evaluated in five rats subjected to 10 minutes of ischemia. After 3 days, the numbers of normal-appearing neurons in the CA1 subregions were counted. Results: Ischemia of 12.5 minutes' duration induced a fourfold increase in serotonin in the hippocampus (mean±SEM baseline, 1.86±0.25 pmol/ml perfusate; during ischemia, 8.14±0.89 pmol/ml; p<0.05 by analysis of variance). Twenty minutes of ischemia induced a 25-fold increase in serotonin in the dorsolateral striatum (baseline, 0.98±0.15 pmol/ml; ischemia, 24.4±5.93 pmol/ml; p<0.001). The histopathological study demonstrated severe ischemic damage in all CA1 subregions of nontreated animals (medial, 34±16 normal-appearing neurons, middle, 52.2±22.9 neurons; lateral, 56.6±21.8 neurons). Treatment with ritanserin significantly attenuated ischemic damage (medial, 117.6±6.5 neurons; middle, 131.4±4.9 neurons; lateral, 130±7.5 neurons; p<0.01 different from nontreated). Conclusions: Taken together, these results suggest that serotonin plays a detrimental role, mediated by 5-HT2 receptors, in the development of ischemic damage.

Original languageEnglish (US)
Pages (from-to)1595-1601
Number of pages7
Issue number11
StatePublished - Nov 1992


  • Cerebral ischemia
  • Rats
  • Ritanserin
  • Serotonin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)


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