Ischemia-induced extracellular release of serotonin plays a role in CA1 neuronal cell death in rats.
OBJECTIVE
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 mg/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.
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival / Q000502:physiology; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology*; D003956:Dialysis / Q000379:methods; D005110:Extracellular Space / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*
D012701:Serotonin; D006897:Hydroxyindoleacetic Acid