Dexamethasone‐induced selective inhibition of the central μ opioid receptor: functional in vivo and in vitro evidence in rodents

Abstract

1 Endogenous corticosteroids and opioids are involved in many functions of the organism, including analgesia, cerebral excitability, stress and others. Therefore, we considered it important to gain information on the functional interaction between corticosteroids and specific opioid receptor subpopulations. 2 We have found that systemic administration (i.p.) of the potent synthetic corticosteroid, dexamethasone, reduced the antinociception induced by the highly selective μ agonist, DAMGO or by less selective μ agonists morphine and β-endorphin administered i.e.v., On the contrary dexamethasone exerted little or no influence on the antinociception induced by a δ₁ agonist, DPDPE and a δ₂ agonist deltorphin II. Dexamethasone potentiated the antinociception induced by the k agonist, U50,488. 3 In experiments performed in an in vitro model of cerebral excitability in the rat hippocampal slice, dexamethasone strongly prevented both the increase of the duration of the field potential recorded in CA1, and the appearance and number of additional population spikes induced by μ receptor agonists. 4 In both models pretreatment with cycloheximide, a protein synthesis inhibitor, prevented the antagonism by dexamethasone of responses to the μ opioid agonists. 5 Our data indicate that in the rodent brain there is an important functional interaction between the corticosteroid and the opioid systems at least at the μ receptor level, while δ and k receptors are modulated in different ways.