Nonopioidergic Mechanism Mediating Morphine-Induced Antianalgesia in the Mouse Spinal Cord

Intrathecal (i.t.) pretreatment with a low dose (0.3 nmol) of morphine causes an attenuation of i.t. morphine-produced an-algesia; the phenomenon has been defined as morphine-in-duced antianalgesia. The opioid-produced analgesia was mea-sured with the tail-flick (TF) test in male CD-1 mice. Intrathecal pretreatment with low dose (0.3 nmol) of morphine time depen-dently attenuated i.t. morphine-produced (3.0 nmol) TF inhibi-tion and reached a maximal effect at 45 min. Intrathecal pre-treatment with morphine (0.009–0.3 nmol) for 45 min also dose dependently attenuated morphine-produced TF inhibition. The i.t. morphine-induced antianalgesia was dose dependently blocked by the nonselective -opioid receptor antagonist ()-naloxone and by its nonopioid enantiomer ()-naloxone, but not by endomorphin-2-sensitive -opioid receptor antagonis