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Serotonergic‐postsynaptic receptors modulate gripping‐induced immobility episodes in male taiep rats
Author(s) -
Eguibar José R.,
Cortés M.C.,
Ita M.L.
Publication year - 2009
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20655
Subject(s) - serotonin , postsynaptic potential , serotonergic , endocrinology , medicine , 5 ht receptor , agonist , serotonin syndrome , psychology , chemistry , neuroscience , receptor
The Taiep rat is a myelin mutant with a motor syndrome characterized by tremor, ataxia, immobility, epilepsy, and paralysis. The rat shows a hypomyelination followed by a progressive demyelination. During immobilities taiep rats show a REM‐like sleep pattern and a disorganized sleep‐wake pattern suggesting taiep rats as a model of narcolepsy‐cataplexy. Our study analyzed the role of postsynaptic serotonin receptors in the expression of gripping‐induced immobility episodes (IEs) in 8‐month‐old male taiep rats. The specific postsynaptic serotonin agonist ±1‐(2,5‐dimethoxy‐4‐iodoamphetamine hydrochloride (±DOI) decreased the frequency of gripping‐induced IEs, but that was not the case with α‐methyl‐serotonin maleate (α‐methyl‐5HT), a nonspecific postsynaptic agonist. Although the serotonin antagonists, ketanserine and metergoline, produced a biphasic effect, first a decrease followed by an increase with higher doses, similar effects were obtained with a mean duration of gripping‐induced IEs. These findings correlate with the pharmacological observations in narcoleptic dogs and humans in which serotonin‐reuptake inhibitors improve cataplexy, particularly in long‐term treatment that could change the serotonin receptor levels. Polysomnographic recordings showed an increase in the awakening time and a decrease in the slow wave and rapid eye movement sleep concomitant with a decrease in immobilities after use of ±DOI, this being stronger with the highest dose. Taken together, our results show that postsynaptic serotonin receptors are involved in the modulation in gripping‐induced IEs caused by the changes in the organization of the sleep‐wake cycle in taiep rats. It is possible that specific agonists, without side effects, could be a useful treatment in human narcoleptic patients. Synapse 63:737–744, 2009. © 2009 Wiley‐Liss, Inc.