Effects of antipsychotic drugs on brain-stimulation detection: preliminary observations

The effects of two antipsychotic drugs, haloperidol and clozapine, on the detection of electrical brain stimulation were investigated. Rats were trained to make an instrumental response to a brain stimulation cue delivered via an electrode implanted in one of several forebrain or midbrain loci. A response to this stimulation was reinforced by the delivery of a rewarding electrical stimulus via a second electrode implanted in the hypothalamus. By varying the current intensity of the cue stimulus, a detection threshold was determined in each subject both prior to and after administration of various doses of haloperidol or clozapine. Compared to changes on vehicle control days, both drugs produced a dose-related elevation of the detection thresholds. Although haloperidol was more potent than clozapine in most subjects, the minimal effective doses of haloperidol for affecting detection from forebrain loci were lower than for affecting detection from midbrain loci. A reverse differential sensitivity was observed after clozapine administration. Concurrent effects of these two drugs on latency to respond, as well as on both task defined strength of responding and ability to inhibit responding not only indicated the specificity of threshold elevations, but provided additional behavioral information concerning the actions of the two antipsychotic agents. It is proposed that the method employed in this experiment is suitable for measuring the effects of drugs on the discriminative or perceptual properties of electrical brain stimulation and may indicate central sites of drug action.