Intrathecal GABA B antagonists attenuate the antinociception produced by microinjection of l-glutamate into the ventromedial medulla of the rat

Abstract

This study examined whether the antinociception produced by glutaminergic stimulation of neurons in the nucleus raphe magnus (NRM) and nucleus reticularis gigantocellularis pars α (NGCpα) is mediated by an action of GABA at GABA B receptors in the spinal cord. Rats were pretreated with intrathecal (i.t.) administration of the selective GABA B receptor antagonists phaclofen (100 μg) or CGP 35348 (30 μg), the serotonin receptor antagonist methysergide (30 μg), or vehicle. Fifteen min later, 30 nmol l-glutamate was microinjected into the NRM, NGCpα, or sites in the medulla outside these two regions. Microinjection of l-glutamate into the NRM or NGCpα in vehicle-pretreated rats significantly increased tail flick latency. This increase was antagonized, but not abolished, by i.t. pretreatment with 30 μg CGP 35348 or 100 μg phaclofen. Pretreatment with 30 μg methysergide completely antagonized the antinociception produced by l-glutamate. Microinjection of l-glutamate at medullary sites outside the NRM or NGCpα did not produce antinociception. In an ancillary experiment, the possibility that the ability of methysergide, phaclofen or CGP 35348 to antagonize glutamate-induced antinociception was related to non-specific increases in tail skin temperature was explored. Although phaclofen or methysergide increased tail skin temperature, the magnitude and time course of this increase were not consistent with the antagonism of glutamate-induced antinociception. Moreover, administration of CGP 35348 resulted in a modest decrease in tail skin temperature. Thus, antagonism of glutamate-induced antinociception does not appear to result from non-specific alterations in tail skin temperature. Taken together, these results indicate that the antinociception produced by activation of neurons in the NRM and NGCpα is at least partially mediated by GABA B receptors in the spinal cord.