Serotonergic-postsynaptic receptors modulate gripping-induced immobility episodes in male taiep rats.
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 alpha-methyl-serotonin maleate (alpha-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.
Eguibar
José R
JR
Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, México. jeguibar@siu.buap.mx
Cortés
M C
MC
Ita
M L
ML
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D046352:Freezing Reaction, Cataleptic / Q000502:physiology*; D008297:Male; D009290:Narcolepsy / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D011922:Rats, Mutant Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use; D012890:Sleep / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin