183 REPEATED AMPHETAMINE ADMINISTRATION ENHANCES ELECTROTONIC TRANSMISSION IN LIMBIC CORTICAL AND STRIATAL REGIONS S.P. Onn*, A.A. G r a c e Department of Neuroscience, Univ. of Pittsburgh, Pittsburgh, PA 15260, USA Evidence suggests that repeated treatment with amphetamine (rAMP) causes persistent augmentation of motor responses mediated by the mesolimbie dopamine (DA) system upon subsequent administration of this drug. The cellular or synaptic mechanisms underlying this sensitization are not yet understood. Using in vivo intracellular recording combined with intracellular injection of the dye Lucifer yellow, we examined whether rAMP administration altered synaptic transmission or dye coupling in DA post-synaptic target cells located in the limbic-related cortical and striatal regions of anesthetized rats. We found that rAMP-treated rats (2-4 mg/kg; i.p. daily for 1-4 wks) exhibited a higher incidence of dye coupling between pyramidal cells in the infralimbic/piriform cortices (rAMP= 5/6 vs basal= 1/6), and between spiny cells in the ventral striatum (rAMP=9/9 vs b a s a l = 2 / l l ) . Dye coupling in the dorsal striatal region (0/6) and the cingulate cortex (0/4) was not altered by rAMP treatment. Acute AMP also failed to alter the coupling incidence in the ventral striatum (0/6). Staining for tyrosine hydroxylase (TH) immunoreactivity revealed higher levels of this enzyme only in the ventral striatum of the rAMP-treated rats. These data suggest that enhanced DA transmission combined with an augmentation of electrical interactions between sets of limbic cortical cells and between ventral striatal cells may be an underlying factor in rAMPinduced behavioral sensitization. Support: NS 19608, MH 42217 & 45156, NARSAD Young Investigator Award. THE SIMULTANEOUS MEASURING OF INFORMATION-PROCESSING DEFICITS AND THOUGHT DISORDER IN SCHIZOPHRENIA William Perry*, Tracy Felger, D a v i d Braff Department of Psychiatry, University of CaliJbrnia at San Diego, 9500 Gilman Drive, La Jolla, CA 92093~7804, USA In order to better understand the relationship between information-processing deficits and thought disorder in schizophrenia, new paradigms are needed. In most studies, thought disordered subjects are rated on the basis of their disturbed thoughts over some extended time-course, and at some later point tested on a psychophysiological measure. The studies have not controlled for fluctuations in thought disorder. To improve upon these paradigmatic shortcomings we have reduced the temporal gap between measuring attentional and information-processing deficits and thought disorder by measuring the production of Rorschach responses (using Perry and Viglione's Eli and Johnston and Holzman's TDI) while measuring either skin conductance orienting responses (SCORs) or sensorimotor gating assessed via prepulse inhibition (PPI) of the human startle response. The findings of our study allow for quantitative and qualitative analyses of the relationship between attention and information processing deficits and thought disorder. Moreover, this design allows us to speculate about the neural circuit abnormalities associated with thought disorder, which have a largely unknown neural basis, and measures of information-processing, which have a better understood neural basis. ~7 N I C O T I N I C R E C E P T O R A N T A G O N I S T S IN THE AWAKE RAT SIMULATE THE AUDITORY GATING DEFICIT FOUND IN SCHIZOPHRENIA Y.D. Rollins*, K.E. Stevens, K. Heman, G.M. Rose, S. L e o n a r d Department of Pharmacology, Box C-268-71, University of Colorado Health Sciences Center, 4200 E. 9th, Denver, CO 80262, USA Schizophrenia is partially characterized by an auditory gating deficit, an abnormal electrophysical response to repeated auditory stimuli that can be temporarily reversed in non-gating humans by treatment with nicotine. A similar gating deficit can be generated in laboratory animals using pharmacological agents. Intracerebroventricular (i.c.v.) injection of a snake venom product, ~-bungarotoxin (c~-BTX), in anesthetized rats causes a loss of auditory gating similar to that seen in schizophrenia, c~-BTX binds to neuronal nicotinic receptors containing the ~7 subunit which is expressed in the geniculate nuclei, the cingulate gyms, the hippocampus, and other sensory associated areas. We have studied the effect of this binding site in vivo by the i.c.v, injection of c~-BTX or methyllycaconitine (MLA), a recently identified ~7 antagonist, followed by recording of electrophysiological response to paired auditory stimuli in the awake rat. Recordings were taken from electrodes implanted on the brain surface and in the CAI and CA3 regions of the hippocampus. Both c~-BTX and MLA caused a reversible reduction in gating. Furthermore, i.c.v, injections of phosphorothioate oligonucleotides complementary to the translation start site of the c~7 neuronal nicotinic receptor subunit caused a similar reduction in gating. These results suggest that the c~7 nicotinic subunit may play a functional role in auditory gating.