Withdrawal from butorphanol dependence alters binding of [3H]phorbol dibutyrate to protein kinase C, but not of [3H]forskolin to adenylate cyclase.

The time course of autoradiographic binding of major second messengers in the rat brain was studied at 2, 7, and 24 h after withdrawal from butorphanol infusion. [3H]Forskolin and [3H]phorbol 12,13-dibutyrate (PDBu) were used to label adenylate cyclase and protein kinase C (PKC), respectively. Rats were rendered dependent by intracerebroventricular infusion of butorphanol (26 nmol microliter-1 h-1) via osmotic minipumps for 3 days. Withdrawal was initiated by abrupt cessation of the butorphanol infusion. The levels of [3H]forskolin binding were not changed at any time or in any brain area, except for an increase following 7 h of withdrawal in the brainstem only. The levels of [3H]PDBu binding were significantly increased (13-47%) in multiple areas of the rat brain following 7 h of withdrawal from butorphanol infusion. These findings suggest that the phosphoinositide cycle system is more susceptible to alteration during butorphanol dependence than is the adenylate cyclase system in the rat brain. Copyright 1999 Elsevier Science B.V.