The effect of antimuscarinic agents on haloperidol induced behavioral hypersensitivity

Varying doses of scopolamine, trihexyphenidyl and benztropine were administered to rats or guinea-pigs by themselves or in combination with 0.5 mg/kg haloperidol for 24 days. All animals were then challenged with 0.75 mg/kg apomorphine and assessed for stereotypic behavior following a 96 h drug free interval. Animals treated with haloperidol alone exhibited behavioral hypersensitivity to apomorphine challenge. Animals treated with both an antimuscarinic agent and haloperidol exhibited a significant reduction in behavioral responsiveness relative to animals treated with only haloperidol. This reduction was directly proportional to the antimuscarinic dose administered. A non-significant trend toward hyposensitivity was observed in animals who had been treated with antimuscarinic agents alone. These results suggest that the development of behavioral hypersensitivity may reflect CNS alterations in cholinergic as well as dopaminergic activity.