Abstract

Intrathecal injection of the analogue of TRH, CG 3509, into conscious rats produced dose-related wet-dog shakes and forepaw licking, which showed a bell-shaped relationship of intensity to dose. Pretreatment with α-MPT intraperitoneally, markedly reduced levels of noradrenaline and dopamine in the spinal cord and brainstem and attenuated both CG 3509-induced responses, while intrathecal treatment with DSP 4 selectively reduced noradrenaline in the spinal cord without affecting either behaviour. Since denervation supersensitivity may develop following treatment with DSP 4, these results are not inconsistent with a proposal that bulbospinal noradrenergic neurones modulate the behaviour induced by CG 3509. Wet-dog shakes and forepaw licking induced by CG 3509 were reduced by pretreatment with phenoxybenzamine or prazosin, suggesting that a tonic noradrenergic pathway may facilitate both behavioural responses through α 1-adrenoceptors. Methoxamine, combined with CG 3509 partially attenuated the wet dog shake behaviour, but methoxamine produced marked hindlimb jerking which might physiologically antagonise wet-dog shakes. Concomitant administration of clonidine and CG 3509 potently reduced wet-dog shakes in a dose-related manner but did not significantly affect forepaw licking, while idazoxan did not significantly affect either response. The latter findings imply that α 2-adrenoceptors play different roles in modulating the two behavioural responses and the possible synaptic location of the receptors is discussed. Taken together these results suggest that CG 3509 may release noradrenaline from bulbospinal neurones regulating motor function.

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