Activation of serotonin 5-HT 1-receptors decreased gripping-induced immobility episodes in taiep rats

Abstract

The taiep rat is a myelin mutant that shows a disorganized sleep–wake cycle and immobility episodes (IEs) when the animals are gripped at the base of the tail. During IEs electroencephalographic recordings show a rapid eye movement (REM) sleep-like pattern. These alterations are quite similar to those reported in narcolepsy–cataplexy. Pharmacologically, systemic administration of α 2 adrenoceptor agonists increases gripping-induced IEs, whereas α 2 antagonists decrease them. However prazosin, an α 1 antagonist, increases gripping-induced IEs. In male 8-month-old taiep rats we have studied the effect of systemic administration of serotonergic autoreceptor agonists and antagonists on gripping-induced IEs. 8-Hydroxy-2-(di- n-propylamino) tetraline hydrobromide (8-OH-DPAT), a 5-HT 1A agonist, and 3-trifluoromethylphenylpiperazine hydrochloride (TFMPP), a 5-HT 1B agonist, produce a significant decrease in the frequency and mean duration of IEs. Systemic administration of spiperone and 1-(2-methoxyphenyl)-4[4-(2-phthalimido) butyl]piperazine hydrobromide (NAN-190), 5-HT 1 antagonists, increase IEs and their mean duration. When the specific serotonin antagonist N-[2[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]- N-2-pyridinyl-cyclohexanecarboxamide maleate (WAY 100635, 100 μg/kg) was injected 15 min before 8-OH-DPAT, this specific antagonist reverses the effects caused by the 5-HT 1A agonist. These results show that serotonergic 5-HT 1-receptors are involved in the susceptibility of gripping-induced IEs in taiep rats. Similar results have been reported in the food-elicited cataplexy test in narcoleptic dogs.