The effects of protection by D-Pen 2-D-Pen 5-enkephalin or D-Ala 2-NMePhe 4-Gly-ol-enkephalin against β-chlornaltrexamine in the spinal cord on the antinociception induced by β-endorphin administered intracerebroventricularly in the mouse

Abstract

Chlornaltrexamine (β-CNA, 0.5 μg) alone or β-CNA plus either μ-agonist, D-Ala 2-NMePhe 4-Gly-ol-enkephalin (DAMGO, 500 ng) or δ-agonist, D-Pen 2-D-Pen 5-enkephalin (DPDPE, 10 μg) was injected intrathecally (i.t.) to protect μ- or δ-opioid receptors, respectively, for 24 h in male ICR mice. The antinociception was assessed by the tail-flick and hot-plate test. DPDPE or DAMGO injected i.t. increased inhibition of the tail-flick and hot-plate response in a dose-dependent manner. The dose-response curve for tail-flick and hot-plate response induced by DPDPE or DAMGO in i.t. saline-treated group significantly shifted to the right in i.t. β-CNA alone treated group but returned to the control level in the group treated with i.t. β-CNA coadministered with DPDPE or DAMGO, respectively. The effects of protection of μ- and δ-opioid receptor in the spinal cord on inhibition of the tail-flick and hot-plate response induced by β-endorphin and morphine administered intracerebroventricularly (i.c.v.) were then studied. Intrathecal pretreatment with β-CNA or β-CNA coadministered with DAMGO attenuated inhibition of the tail-flick response induced by β-endorphin administered i.c.v. However, i.t. treatment with β-CNA coadministered with DPDPE did not affect inhibition of the tail-flick response induced by β-endorphin administered i.c.v. Intrathecal pretreatment with β-CNA or β-CNA coadministered with either DPDPE or DAMGO did not alter inhibition of the hot-plate response induced by β-endorphin administered i.c.v. Intrathecal injection of β-CNA alone did not affect inhibition of the tail-flick and hot-plate response induced by morphine given i.c.v. The results suggest that spinal δ- but not μ-opioid receptors are involved in inhibition of the tail-flick response induced by β-endorphin given i.c.v. On the other hand, inhibition of the tail-flick and hot-plate response induced by morphine given i.c.v. is not mediated through spinal opioid receptors.