Withdrawal from butorphanol dependence alters binding of [H]phorbol dibutyrate to protein kinase C, but not of [H]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 μl⁻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.