ABSTRACT

The effect of dexamethasone (dex) and its interaction with morphine has been studied on analgesia in mice.

DEX i.p. pretreatment reduced analgesic responses to morphine injected 120 min but not 10 min after dexamethasone; i.c.v. injection of DEX 10 and 120 min before morphine administration was effective in reducing morphine analgesia. RU 38486 i.c.v. pretreatment (but not i.p. pretreatment) performed 120 (but not 10) min before morphine administration enhanced morphine analgesic effects.

Also, DEX reduced the antinociception induced by the highly selective mu agonist, DAMGO or by less selective (mu agonists morphine and beta endorphin administered i.c.v.). On the contrary, DEX exerted little or no influence on the antinociception induced by a delta1 agonist, DPDPE and delta2 agonist deltorphin II. DEX potentiated the antinociception induced by the k agonist, U50, 488.

Pretreatment with cycloheximide, a protein synthesis inhibitor, prevented the antagonism by DEX of responses to the mu opioid agonists. Finally, i.c.v. injection of DEX significantly reduced morphine analgesia in Swiss mice whereas no effects were observed in DBA/2J and C57BL/6 mice. In addition, i.p. injection of DEX significantly reduced morphine analgesia in all three strains.

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 mu.  receptor level,  while delta and k receptors are modulated in different ways. These results, particularly the effects of drug interaction for i.c.v. administration, strongly confirm a central site for DEX and RU 38486 action as well as the use of different genetic strains may provide an useful approach for studying DEX-morphine analgesia interaction.