Effects of intravenously administered enantiomers of baclofen on functionally identified units in lumbar dorsal horn of the spinal cat
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abstract
The present study investigated the effects of intravenous administration of the d- and l-enantiomers of baclofen on extracellular single unit spikes recorded from the lumbar dorsal horn of the spinalized cat, either anaesthetized with chloralose or decerebrated. Both enantiomers had two types of depressant effect. One was a transient (complete within 2 min), non-specific depression of the discharge of synaptically-elicited responses and of the postsynaptic glutamate-evoked excitation; it is reasoned that this effect was due to a postsynaptic action of baclofen and its antagonism by bicuculline suggests it is via classical GABA receptors. The other type of depression was more prolonged, lasting usually for more than 1 hr. It was observed as a preferential blocking of spontaneous activity, as well as of evoked responses to noxious stimuli or innocuous thermal stimuli applied to the skin, with little or no effect on responses to hair movement or to the iontophoretic application of glutamate. In addition, baclofen preferentially reduced the late, higher threshold component of evoked responses of wide dynamic range neurones to electrical stimulation of the cutaneous receptive field. Thus, whether tested on naturally- or electrically-evoked responses, baclofen had a preferential effect on those mediated by small diameter afferents. Doses giving approximately equal effects were 0.1 mg/kg for l-baclofen and 10 mg/kg for d-baclofen. The results of the present study support recent evidence of a prolonged antinociceptive effect of baclofen, indicate that at least some of this effect is mediated by an action at the spinal level and support the possibility that the action is presynaptic, perhaps on the terminals of primary afferent fibres. In addition, a similar mechanism may account for the depression of spinal polysynaptic reflexes and thus, perhaps, additionally for some of the antispastic properties of baclofen.
