Butorphanol, a synthetic agonist/antagonist, has been shown to act on
mu-, delta- and kappa-Opioid receptors. However, the relative involvem
ent of opioid receptor subtypes in mediating butorphanol dependence is
not known. In the present study, naltrindole, a delta-selective non-p
eptide antagonist, was administered intracerebroventricularly (i.c.v.)
to mask supraspinal delta-opioid receptors before and during the indu
ction of butorphanol dependence. Treatment with naltrindole (0.1, 1, o
r 10 nmol/5 mul per rat) significantly blocked naloxone-, a nonspecifi
c antagonist, precipitated butorphanol withdrawal behaviors (escape be
havior, teeth-chattering, wet shakes, forepaw tremors, ptosis, diarrhe
a, body weight loss, and hypothermia) at all doses tested, and decreas
ed ejaculation at 0.1 nmol in butorphanol-infused rats. In contrast, n
altrindole treatment had no effect on yawning, nor urination. These re
sults indicate that central delta-opioid receptors are involved in med
iating butorphanol dependence in rats.