Differential Mechanisms of Antianalgesia Induced by Endomorphin-1 and Endomorphin-2 in the Ventral Periaqueductal Gray of the Rat

The effects of pretreatment with endomorphin-1 (EM-1) and en-domorphin-2 (EM-2) given into the ventral periaqueductal gray (vPAG) to induce antianalgesia against the tail-flick (TF) inhibition produced by morphine given into the vPAG were studied in rats. Pretreatment with EM-1 (3.5–28 nmol) given into vPAG for 45 min dose-dependently attenuated the TF inhibition produced by mor-phine (9 nmol) given into vPAG. Similarly, pretreatment with EM-2 (1.7–7.0 nmol) for 45 min also attenuated the TF inhibition induced by morphine; however, a high dose of EM-2 (14 nmol) did not attenuate themorphine-produced TF inhibition. The attenuation of morphine-produced TF inhibition induced by EM-2 or EM-1 pre-treatment was blocked by pretreatment with -opioid antagonist ()-naloxone (55 pmol) but not nonopioid ()-naloxone (55 pmol). However, pretreatment with a morphine-6-glucuronide-sensitiv