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 studi es suggesting that intermittent neuroleptic treatment may increase the risk of irreversible TD in humans and persistent vacuous chewing move ments (VCM) in rats. We investigated the effect of daily intracerebrov entricular (ICV) injections of haloperidol 37.5 mu g/kg for 12 weeks i n rats. Behavior was recorded immediately after the first injection, w ith 2 weeks intervals during treatment, and 3 weeks after drug withdra wal. In a separate experiment, rats received one injection of haloperi dol IF. 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 mu ch longer duration. No significant behavioral changes were observed ei ther 24 h after the ICV injections during haloperidol treatment or 3 w eeks after drug withdrawal. The results did not support the hypothesis that kindling is important for the development of TD.