Acute and chronic effects of intrathecal galanin on behavioural and biochemical markers of spinal motor function in adult rats

Abstract

The spinal motor effects of galanin, which co-exists with 5-hydroxytryptamine (5-HT) and thyrotrophin-releasing hormone (TRH) in bulbospinal raphe neurones innervating spinal motoneurones, were examined by administering this neuropeptide through indwelling intrathecal cannulae to conscious adult Wistar rats. The acute effect of intrathecal galanin on spontaneous motor behaviour and the motor behaviours (back muscle contractions and wet-dog shakes) elicited by intrathecal injection of the non-selective 5-HT receptor agonist, 5-methoxy-N, N′-dimethyltryptamine (5-MeODMT) or the TRH analogue, RX 77368 (pGlu-His-3, 3′-dimethyl-ProNH 2), respectively, and the chronic effect of galanin on neurochemical markers for bulbospinal raphe neurones and spinal motoneurones were determined. Intrathecal galanin (0.1 to 10 μg) did not produce any notable motor behaviours when given alone, but pretreatment with the neuropeptide (0.1 μg) significantly attenuated both the number of wet-dog shakes and the amount of forepaw-licking induced by RX 77368, without affecting 5-MeODMT-induced back muscle contractions. Repeated intrathecal galanin administration (1 μg, twice daily for 5 d) significantly elevated 5-HT (but not 5-hydroxyindoleacetic acid) and substance P-like immunoreactive (LI) levels and choline acetyltransferase (ChAT) activity in the dorsal, but not in the ventral, portion of the thoraco-lumbar spinal cord. In contrast, chronic intrathecal galanin did not alter the TRH- or calcitonin gene-related peptide (CGRP)-LI levels in either spinal cord regions. As expected if endogenous galanin modifies sensory afferent information, intrathecal injection decreased the release and/or increased the metabolism of both 5-HT and substance P in the dorsal horn where these neurotransmitters are thought to be involved in processing sensory information. Intrathecal galanin attenuated RX 77368-induced forepaw-licking and wet-dog shakes but as neither of these behaviours are altered by destruction of bulbospinal raphe neurones this effect may not involve an action of galanin on spinal motoneurones; some possible sites of interaction are discussed. The lack of effect of intrathecal galanin on 5-MeODMT-induced back muscle contractions, a spinally mediated motor behaviour, and the absence of any change in neurochemical markers for either bulbospinal raphe neurone terminals (ventral horn 5-HT, TRH and substance P levels) or spinal motoneurones (ChAT activity and CGRP-LI) suggest that this neuropeptide has little direct effect on the control of normal spinal motor function in the adult rat.