A new animal model of dopamine supersensitivity using s.c. implantation of haloperidol releasing polymers.

Dopamine supersensitivity was induced by either the continuous daily release of 1.0 mg/kg haloperidol from controlled release polymers implanted subcutaneously in rats or by daily bolus injection. In vitro, these polymers were found to release haloperidol for more than 250 days. After implantation in vivo, supersensitivity was quantified by locomotor activity following apomorphine injection and specific [3H]spiroperidol binding to striatal synaptic membranes. Supersensitivity in rats with haloperidol implants was remarkably similar to that evoked by daily drug applications after 3 weeks without producing the detrimental daily sedations, typically seen after bolus administration. Furthermore, no difference in specific binding between both group was seen. A continuous delivery of haloperidol for 8 weeks also resulted in comparable denervation supersensitivity. Controlled release polymers may thus be a superior tool to induce denervation supersensitivity in a gradual, continuous fashion.