Presynaptic dopaminergic agonists increased gripping-generated immobility episodes in the myelin-mutant taiep rat

Abstract

The taiep rat is a myelin mutant whose immobility episodes (IEs) can be caused by gripping them by the tail. Electroencephalographic recordings during IEs show a rapid-eye movement sleep-like pattern, similar to narcolepsy-cataplexy in canines. Systemic administration of α 2-adrenoceptor agonists and the α 1 antagonist increase gripping-generated IEs. Furthermore, adrenergic α 2 antagonists decrease them. Serotonin receptors are also involved in the regulation of IEs, because the 5-HT 1A-5-HT 1B serotonin-receptor agonists decrease the IE frequency, as do the postsynaptic-serotonergic 5-HT 2A–2C agonists. The rats were maintained under standard conditions with a 12:12 h light:dark cycle, lights on at 0700, with free access to rodent pellets and tap water. Drugs were freshly prepared using sterile water and administered intraperitoneally at 0800 with the observation lasting 90 min. The IEs were caused by gripping the rat's tail every 5 min. Systemic injection of (−)-quinpirole, R(+)-7-hydroxy-2-(dipropylamino)tetralin (7-OH-DPAT), or trans-(±)-3,4,4a,10b-Tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4,3-b]-1,4-oxazin-9-ol ((±) PD 128,907) increased both the frequency and mean duration of the IEs. The IEs produced by (−)-quinpirole were blocked by the previous administration of (−)-sulpiride and those by 7-OH-DPAT were blocked by tiapride. Systemic injection of sulpiride reduced gripping-generated IEs, but not the changes with either tiapride or U-99194, two other antagonists. In canine narcolepsy, systemic administration of D 2-dopaminergic agonists increases the frequency of cataplexies and decreased them by using (−)-sulpiride similar to the pharmacological profile in taiep cataplexies. Because of this evidence, we proposed taiep rats as an adequate model of this sleep illness and for the evaluation of anticataplexic drugs.