A dietary haloperidol regimen for inducing dopamine receptor supersensitivity in rats

The induction of dopaminergic supersensitivity in rats by the administration of haloperidol in their diet for 30 days (CHAL) in three increasing concentrations (7-15 mg/kg/day) was compared to that induced by single daily subcutaneous injections (SCHAL, 0.7 mg/kg) on the basis of biochemical (radioimmunoassay of serum haloperidol levels, 3H-spiroperidol binding) or behavioral (apomorphine stereotypy, spontaneous locomotor activity) parameters. The two modes of administration produced equivalent blood levels of haloperidol by day 30. At 48 hours post treatment: spontaneous locomotor activity and stereotyped behavior were significantly increased in both groups of haloperidol-treated rats, stereotyped behavior was significantly greater in CHAL- vs. SCHAL-treated rats at 8 days post treatment and specific 3H-spiroperidol binding was increased 64% and 236% within the striatum and GP, respectively, of CHAL-treated vs. control rats. Scatchard analysis of 3H-spiroperidol binding isotherms revealed a significant increase in the Bmax of high affinity binding sites [KD approximately 55 pM] within the striatum of both CHAL- and SCHAL-treated rats at 48 hours post treatment. A second, lower affinity site was resolved within the SCHAL-treated group which was not detected within striatal homogenates of CHAL-treated or control rats.