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Monoaminergic influences on various inhibitions of the spinal monosynaptic reflex

University of British Columbia

The functional significance of bulbospinal 5-hydroxytryptamine (5-HT) and noradrenaline neurones is not well understood. Therefore in this study, the effects of various drugs that alter monoaminergic synaptic activity were tested on bulbospinal, presynaptic, recurrent and reciprocal la inhibitions of an extensor (quadriceps, QUAD) and a flexor (posterior biceps-semitendi-nosus, PBST) monosynaptic reflex (MSR) in unanaesthetized decerebrate cats. The following agents were employed in the investigation: a biogenic amine neuronal uptake blocker, imipramine HCI (0.125 - 5 mg/kg); a 5-HT neuronal uptake blocker, fluoxetine HCI (Lilly 110140, 0.25 - 6 mg/kg); a 5-HT precursor, 5-hydroxytryptophan (75 mg/kg); a tryptophan hydroxylase inhibitor that depletes 5-HT, DL-p-chlorophenylalanine (300 mg/kg i.p., injected on two consecutive days before the experiment); a tyrosine hydroxylase inhibitor that depletes noradrenaline, DL-a-methyl-p_-tyrosine methyl ester HCI (125 mg/kg i.p., administered 16 and 4 hours prior to the experiment) ; a 5-HT antagonist, cyproheptadine HCI (2.5 - 5 mg/kg); an adrenergic blocker, phenoxybenzamine HCI (2.5 - 5 mg/kg); and clonidine (2.5 - 40 μ g/kg), reported to be a specific a-adrenergic agonist. A thoracic cold block, which prevents supraspinal inputs to the caudal spinal cord, was applied to test whether a drug acts through the descending systems and to determine if the inhibitions of the MSR under study are influenced by the supraspinal tonic pathways. The physiological and the pharmacological studies have led to the following conclusions: presynaptic and recurrent inhibitions of the QUAD- but not of the PBST-MSR are under a tonic inhibitory influence of a descending system which involves 5-HT and noradrenaline; bulbospinal inhibition of the QUAD-MSR involves both presynaptic and postsynaptic types of inhibition and both types of inhibition are antagonized by a tonically active 5-HT system; a tonically active descending system antagonizes reciprocal la inhibition of the extensor but not of the flexor reflex; the excitability of QUAD la afferents is decreased by a descending tonically active 5-HT system; and a tonically active supraspinal system has an overall excitatory influence on the extensor motoneurones. Imipramine was more potent in antagonizing bulbospinal and recurrent inhibitions of the MSR when administered intra-arterially to the spinal cord than when injected intravenously or intra-arterially to the brain stem. Therefore, the 5-HT nerve terminals proposed to be involved in antagonizing bulbospinal and recurrent inhibitions are likely located in the spinal cord. Clonidine antagonized all the inhibitions of the extensor and the flexor MSRs tested in this study. However, iontophoretically applied clonidine blocked the depressant effects of glycine and γ-aminobutyric acid on approximately 50% of the spinal neurones tested. This finding suggests that clonidine is not a specific α-adrenergic agonist and may have blocked the inhibitions by antagonizing glycine and γ-aniinobutyric acid.

Text

2010-02-12

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http://hdl.handle.net/2429/20179

Pharmaceutical Sciences

University of British Columbia

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