Comparison of Effects of Various Types of NA and 5‐HT Agonists on Transmission from Group II Muscle Afferents in the Cat

Abstract

A number of noradrenaline and serotonin agonists were tested to investigate which of them replicate the depressive actions of monoamines on transmission from group II muscle afferents in the cat spinal cord. The agonists were applied ionophoretically at the two sites at which maximal monosynaptic focal field potentials are evoked from group II afferents-in the intermediate zone and the dorsal horn of the 4th and 5th lumbar segments. Their effects were estimated from changes in the amplitude of the field potentials. The compounds tested fell into three categories according to the site at which they depressed transmission from group II afferents: one category with highly selective actions in the intermediate zone, a second category with similarly selective actions in the dorsal horn, and a third category with non-selective actions. Drugs in the first category included three noradrenaline agonists (tizanidine, B-HT 933 and clonidine), included in the second were five serotonin agonists (8-OH-DPAT, 5-methoxytryptamine, alpha-methyl serotonin, DOI and 2-methyl-serotonin), and in the third two noradrenaline agonists (phenylephrine and isoproterenol) and two serotonin agonists (RU 24969 and 5-carboxamidotryptamine). Field potentials evoked by group I afferents remained unaffected by all but one compound (8-OH-DPAT). Effects of one noradrenaline agonist and one serotonin agonist (tizanidine and 5-methoxytryptamine) were also tested on responses of single extracellularly recorded neurons. Tizanidine depressed responses induced by stimulation of group II afferents in intermediate zone interneurons, but not in dorsal horn neurons, while 5-methoxytryptamine depressed activation of the latter. Tizanidine had no effect on responses evoked by group I afferents, either in intermediate zone interneurons or in the dorsal spino-cerebellar tract neurons of Clarke's column. It is hypothesized that noradrenaline and serotonin released by descending monoaminergic neurons differ in the potency with which they depress transmission from group II afferents to different functional types of neuron. The results suggest that this depression may involve different membrane receptors at different locations, primarily alpha2 adrenoceptors in the intermediate zone/ventral horn and 5-HT1A serotonin receptors in the dorsal horn.

Spatial and temporal patterns of serotonin release in the rat’s lumbar spinal cord following electrical stimulation of the nucleus raphe magnus

“…In lamina VII of the cat, both substances facilitate the activation by reticulospinal fibers of commissural neurons involved in interlimb coordination, whereas their activation by group II fibers is blocked by norepinephrine and facilitated by serotonin (Hammar et al, 2004). The differences likely depend on the receptor subtypes involved and their presynaptic or postsynaptic locations (Bras et al, 1990;Maxwell et al, 2003;Dougherty et al, 2005), which remain poorly delineated. Among serotonin subtypes, 5-HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 3 and 5-HT 7 all seem to be important for spinal motor function (Schmidt and Jordan, 2000;Hochman et al, 2001), and among catecholamine receptor subtypes α 1 , α 2A and α 2C may all be critical (Bras et al, 1990).…”

“…The differences likely depend on the receptor subtypes involved and their presynaptic or postsynaptic locations (Bras et al, 1990;Maxwell et al, 2003;Dougherty et al, 2005), which remain poorly delineated. Among serotonin subtypes, 5-HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 3 and 5-HT 7 all seem to be important for spinal motor function (Schmidt and Jordan, 2000;Hochman et al, 2001), and among catecholamine receptor subtypes α 1 , α 2A and α 2C may all be critical (Bras et al, 1990). The detection threshold of our measurements (5-10 nM) was above the K m of most 5-HT receptor subtypes.…”

Spinal Cord-Transected Mice Learn to Step in Response to Quipazine Treatment and Robotic Training

“…Furthermore, numerous findings associate 5-HT with sensory input modulation (Machacek et al, 2001;Meuser et al, 2002;Miquel et al, 2002;Shay and Hochman, 2002;Bosco et al, 2003;Hains et al, 2003). In intact cats, monoamine release selectively increases the excitability of some reflex circuits but decreases the excitability of others, e.g., potentiating transmission from group I spindle fibers and tendon organs (Edgley et al, 1988;Bras et al, 1990) while depressing transmission from nociceptors and group II fibers (Headley et al, 1978; Figure 5. Progression of locomotor performance attributable to administration and withdrawal of quipazine during continued robotic training.…”

Spinal 5‐HT‐receptors and tonic modulation of transmission through a withdrawal reflex pathway in the decerebrated rabbit

“…There is much debate on the roles of 5-HT receptors in general, and 5-HTIA-receptors in particular, in controlling transmission through the spinal cord. Most of the evidence supporting a role for 5-HT in tonic descending inhibition is based on the effects of the non-selective 5-HTI/2-receptor antagonist/partial agonist drug methysergide (Engberg et al, 1968;Rivot et al, 1987; see Duggan & Morton, 1988 (Nagano et al, 1988;Zemlan et al, 1988;Bras et al, 1990;Jackson & White, 1990;Wang & Dun, 1990;Crick & Wallis, 1991;Bervoets et al, 1993;Alhaider & Wilcox, 1993;Ali et al, 1994;Clarke et al, 1994;Hasegawa & Ono, 1996; see also Cesselin et al, 1994;Millan, 1995). Inhibitory effects of 5-HTIA-receptor agonists have been most commonly observed on responses evoked by stimulation of low-threshold afferent fibres.…”

“…Further, 5-HT has profound effects on reflex function (e.g. Anden et Bras et al, 1990;Crick & Wallis, 1991) and crucially, there are a number of studies implicating 5-HT as a mediator of tonic descending control of spinally-mediated events (Engberg et al, 1968;Rivot et al, 1987, see also Duggan, 1985;Fields et al, 1991).…”