Hypophysectomy may non-selectively alter pharmacokinetic parameters to enhance the ability of haloperidol to increase striatal dopamine receptor density in the rat.

We have investigated the effect of a range of doses of haloperidol (0.625-5.0 mg/kg/day) or saline, administered for 14 days, followed by a 3 day drug washout period, to sham operated or hypophysectomized rats. Haloperidol increased the number of specific striatal 3H-spiperone binding sites (Bmax) in sham-operated animals at doses of 2.5 and 5.0 mg/kg/day, and in hypophysectomized animals at all doses used (0.625-5.0 mg/kg/day). The inhibition of locomotor activity produced by haloperidol was greater in hypophysectomized than sham-operated animals. Plasma and striatal haloperidol levels after equivalent doses were greater in hypophysectomized than in sham-operated animals. We conclude that hypophysectomy may enhance the ability of haloperidol to induce striatal dopamine receptor supersensitivity in the rat, and that this may be due to differences in the pharmacokinetic handling of haloperidol between sham-operated and hypophysectomized animals.