Abstract
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.
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