Spinal effects of chronic intrathecal administration of the thyrotrophin-releasing hormone analogue (CG 3509) in rats.
The effect of repeated intrathecal administration of a thyrotrophin-releasing hormone (TRH) analogue (CG 3509; 2 micrograms twice daily for 5 days) on wet-dog shake (WDS) and forepaw-licking (FPL) behaviours and spinal cord TRH and indoleamine levels and choline acetyltransferase (ChAT) activity was examined in adult rats. A rapid behavioural tolerance developed to repeated intrathecal injections of CG 3509; WDS and FPL behaviours were reduced by 57% and 34%, respectively, following the fifth injection and remained reduced at the ninth injection. Repeated CG 3509 administration selectively elevated ChAT activity and the level of 5-hydroxytryptamine (5-HT) in the ventral but not in the dorsal horn of the spinal cord, while 5-hydroxyindoleacetic acid (5-HIAA) and TRH levels were unaltered in either region. As ventral horn ChAT activity is principally located within motoneurones this data implies that TRH exerts a trophic-like influence on mature rat motoneurones in vivo. The results also suggest that long-term intrathecal TRH administration may decrease the release of 5-HT from bulbospinal raphe neurones.
Fone
K C
KC
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham, U.K.
Dix
P
P
Tomlinson
D R
DR
Bennett
G W
GW
Marsden
C A
CA
D000818:Animals; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007278:Injections, Spinal; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012701:Serotonin / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013239:Stereotyped Behavior / Q000187:drug effects; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
C036430:orotirelin; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D013973:Thyrotropin-Releasing Hormone; D002795:Choline O-Acetyltransferase