Aldes has recently demostrated that an area of the rat cortex contains neurons which, upon discrete electrical microstimulation, cause contractions of the tongue. The same cortical area also contains neurons which send their axons to a region of the caudate nucleus which is latero-dorsal and enlarges ventro-laterally as the sections become more caudal. We have been very intrigued by the fact that neuroleptic (NL)-induced so-called tardive dyskinesia affects predominantly the oro-lingual muscles. One possibility is that dopamine (DA) receptors in this caudate region may be more sensitive to DA or may develop DA supersensitiveness to NL administration more easily than receptors elsewhere within the neostriatum. An alternative possibility is that DA receptors in this zone are more densely distributed than elsewhere within the neostriatum. We propose to test the correctness of thes hypotheses by means of electrophysiological and receptor tagging studies. The electrophysiological setting will involve recordings of field potentials (FP) and unitary potentials within and outside of the caudate projection zone in experimentally naive rats and in rats which have been subjected to a protracted period (six months) of NL administration. The presence of FP will be noted and signal averaged. Unitary activity will be fed into a Data Analysing System to obtain interval histograms (IH) during spontaneous firing and post-stimulus time histograms (PSTH) of transynaptic responses to single pulse electrical stimulation of the projection cortex. Through the same multibarrel assembly, FP, IH and PSTH will be systematically subjected to microiontophoresis of DA, haloperidol, ACh, glutamate, and ketamine to determine their effects and to characterize the receptor sensitiveness of the field or unitary potential under scrutiny. The effects of the iontophorized substances on the amplitude, duration, and configuration of the FP will be documented. Dose-response curves will be obtained for the unitary activity. A record of sterotaxic tracks will be kept to map the points of each discharge. To determine the distribution of DA receptors, the animals will be decapitated, the brains removed and fresh frozen sections will be obtained in a cryostat. Sections will be mounted onto slides, incubated and tritiated with haloperidol, and analyzed with standard antoradiographic methods.
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