Administration of the 5-hydroxytryptamine(1A) receptor antagonist WAY100635 suppresses acute experimental allergic encephalomyelitis in Lewis rats.
Experimental allergic encephalomyelitis (EAE) is a T-cell inflammatory disease of the central nervous system (CNS) widely considered as an animal model of multiple sclerosis. In Lewis rats, myelin basic protein-complete Freund's adjuvant (MBP-CFA)-induced EAE is an acute monophasic disease from which animals recover fully. In our experiments, daily treatment (since day 1 after MBP-CFA inoculation) with the 5-hydroxytryptamine((1A)) (5-HT(1A)) receptor agonist (R)-(+)-8-hydroxy-2-(Dipropylamino)-tetralin (R(+)-8-OH-DPAT) resulted in a dose-related enhancement of neurological and histological signs in EAE-induced rats. This effect of R(+)-8-OH-DPAT was reduced by the co-administration of the 5-HT(1A) receptor antagonist (N-[2-(4-[2-mehoxyphenil]-1-piperazinyl)-ethyl]-N-2-pyridinylcyclohexanecarboxamide (WAY100635) at the peak of the acute disease. Moreover, treatment with WAY100635 since inoculation resulted in a delayed onset of the first clinical signs, milder disease and earlier regression of neurological signs along with a decrease in inflammation in the CNS.
Neuroimmunology Laboratory, Department of Pharmacology, School of Medicine, C/ San Francisco, s/n. 15782 Santiago de Compostela, A Coruña, Spain. fffregar@usc.es
Manuel
M
Freire-Garabal
María J
MJ
Núñez
José
J
Balboa
Luis A
LA
García-Vallejo
Sonia
S
Argibay
Elena
E
Rodrigo
Manuel
M
Rey-Méndez
D000208:Acute Disease; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D006967:Hypersensitivity; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*
D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide