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.