Activation of serotonin 5-HT1-receptors decreased gripping-induced immobility episodes in taiep rats.

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 alpha(2) adrenoceptor agonists increases gripping-induced IEs, whereas alpha(2) antagonists decrease them. However prazosin, an alpha(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 microg/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.

Characterization of the spontaneous and gripping-induced immobility episodes on taiep rats.

In 1989, we described a new autosomic-recessive myelin-mutant rat that develops a progressive motor syndrome characterized by tremor, ataxia, immobility episodes (IEs), epilepsy, and paralysis. taiep is the acronym of these symptoms. The rat developed a hypomyelination, followed by demyelination. At an age of 7-8 months, taiep rats developed IEs, characterized electroencephalographically by REM sleep-like cortical activity. In our study, we analyzed the ontogeny of gripping-induced IEs between 5 and 18 months, their dependence to light-dark changes, sexual dimorphism, and susceptibility to mild stress. Our results showed that IEs start at an age of 6.5 months, with a peak frequency between 8.5 and 9.5 months. IEs have two peaks, one in the morning (0800-1000 h) and a second peak in the middle of the night (2300-0100 h). Spontaneous IEs showed an even distribution with a mean of 3 IEs every 2 h. IEs are sexually dimorphic being more common in male rats. The IEs can be induced by gripping the rat by the tail or the thorax, but most of the IEs were produced by gripping the tail. Mild stress produced by i.p. injection of physiological saline significantly decreased IEs. These results suggested that IEs are dependent on several biological variables, which are caused by hypomyelination, followed by demyelization, which causes alterations in the brainstem and hypothalamic mechanisms responsible for the sleep-wake cycle regulation, producing emergence of REM sleep-like behavior during awake periods.