Differential effect of dexamethasone on the antinociception induced by GABA receptor agonists or glutamate receptor antagonists administered spinally in the mouse

It is not well identified that effect of dexamethasone in the antinociception, when administered spinally as well as its interaction with GABAergic and glutamatergic systems. We investigated to determine the possible role of glucocorticoid in the regulation of the anti-nociception induced by GABA receptor agonists and glutamate receptor antagonists treated spinally, using the tail-flick test. Mice were injected i.t. with a dose of dexamethasone (400 ng) in the presence or absence of muscimol (100 ng), baclofen (10 ng), MK-801(2 mug), or CNQX (1 mug). When dexamethasone was co-administered spinally with muscimol or CNQX, the antinociceptive response was synergistically increased. Mice were pretreated with yohimbine (from 1 to 20 mug), methysergide (from 1 to 20 mug), or naloxone (from 0.1 to 2 mug). And then, muscimol plus dexamethasone or CNQX plus dexamethasone was injected i.t. The pretreatment with yohimbine, methysergide, or naloxone attenuated the inhibition of the tail-flick response induced by muscimol plus dexamethasone or CNQX plus dexamethasone in a dose-dependent manner. It is suggested that spinal alpha (2)-adrenergic and serotonergic receptors may be involved in spinally administered dexamethasone plus muscimol as well as dexamethasone plus CNQX. Also, it is speculated that opioids can be released by administration of dexamethasone plus muscimol or CNQX, and then stimulation of opioid receptors may be responsible for the synergistic antinociceptive interaction observed between glucocorticoid and GABA,, or non-NMDA system.