Tardive dyskinesia: behavioral effects of repeated intracerebroventricular haloperidol injections in rats do not confirm the kindling hypothesis.

The development of tardive dyskinesia (TD) has been claimed to be the result of a kindling-like mechanism. This hypothesis is based on studies suggesting that intermittent neuroleptic treatment may increase the risk of irreversible TD in humans and persistent vacuous chewing movements (VCM) in rats. We investigated the effect of daily intracerebroventricular (ICV) injections of haloperidol 37.5 micrograms/kg for 12 weeks in rats. Behavior was recorded immediately after the first injection, with 2 weeks intervals during treatment, and 3 weeks after drug withdrawal. In a separate experiment, rats received one injection of haloperidol IP. The acute effect of haloperidol ICV was an immediate increase in VCM and a reduction in motor activity that lasted for approximately 2 h. The behavioral response to haloperidol IP was similar, but of much longer duration. No significant behavioral changes were observed either 24 h after the ICV injections during haloperidol treatment or 3 weeks after drug withdrawal. The results did not support the hypothesis that kindling is important for the development of TD.