caa a22 4500 469121017 CHVBK 20180323133138.0 cr unu---uuuuu 170328e19920101xx s 000 0 eng 10.1007/BF02253587 doi (NATIONALLICENCE)springer-10.1007/BF02253587 Effect of haloperidol and clozapine on the density of "perforated” synapses in caudate, nucleus accumbens, and medial prefrontal cortex [Elektronische Daten] [Charles Meshul, Aaron Janowsky, Daniel Casey, Regina Stallbaumer, Barry Taylor] Perforated synapses, which contain a discontinuous density along the postsynaptic membrane, can increase or decrease in numbers following various behavioral and biochemical manipulations. We have previously established that 14-day treatment with haloperidol causes an increase in the number of perforated synapses within the caudate nucleus (dorsolateral region) but not the nucleus accumbens (Meshul and Casey 1989). This effect was reversed if the animals were withdrawn from the drug for an equivalent period of time. We have now further examined the effects of haloperidol administration, which is associated with a high incidence of extrapyramidal side effects (EPS) and tardive dyskinesia (TD), and assessed the effects of clozapine, which appears to have a lower potential for inducing EPS and TD. Administration of haloperidol for 2 weeks significantly increased the percentage of perforated synapses in the caudate, but not in the nucleus accumbens or layer VI of medial prefrontal cortex (MPCx). There was an increase in specific [125I]epidepride binding to D-2 receptors in the caudate nucleus and MPCx following haloperidol. Administration of clozapine for 2 weeks did not affect the percentage of perforated synapses in any of the three dopamine (DA)-rich regions that were examined. There was an increase in specific [3H]SCH 23390 binding to D-1 receptors and in specific [125I]epidepride binding to D-2 receptors only within MPCx following clozapine. The absence of any change in the density of perforated synapses within the dorsolateral caudate nucleus following clozapine correlates with: 1) the lack of effect on specific DA receptor binding or down regulation of serotonin (5-HT2) receptors (as reported by others), or 2) the inability in clozapine-treated animals to depolarize block substantia nigra (A9) DA neurons. These results may be related to the low incidence of EPS and TD observed with clozapine. Springer-Verlag, 1992 Haloperidol nationallicence Clozapine nationallicence Perforated synapses nationallicence Electron microscopy nationallicence Tardive dyskinesia nationallicence Extrapyramidal syndrome nationallicence Meshul Charles Laboratory, V.A. Medical Center, The Oregon Health Sciences University, 3710 S.W. Veterans Hospital Road, 97201, Portland, OR, USA aut Janowsky Aaron Research Services, V.A. Medical Center, The Oregon Health Sciences University, 3710 S.W. Veterans Hospital Road, 97201, Portland, OR, USA aut Casey Daniel Research Services, V.A. Medical Center, The Oregon Health Sciences University, 3710 S.W. Veterans Hospital Road, 97201, Portland, OR, USA aut Stallbaumer Regina Research Services, V.A. Medical Center, The Oregon Health Sciences University, 3710 S.W. Veterans Hospital Road, 97201, Portland, OR, USA aut Taylor Barry Research Services, V.A. Medical Center, The Oregon Health Sciences University, 3710 S.W. Veterans Hospital Road, 97201, Portland, OR, USA aut Psychopharmacology Springer-Verlag 106/1(1992-01-01), 45-52 0033-3158 106:1<45 1992 106 213 https://doi.org/10.1007/BF02253587 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF02253587 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Meshul Charles Laboratory, V.A. Medical Center, The Oregon Health Sciences University, 3710 S.W. Veterans Hospital Road, 97201, Portland, OR, USA aut NATIONALLICENCE 700 1- Janowsky Aaron Research Services, V.A. Medical Center, The Oregon Health Sciences University, 3710 S.W. Veterans Hospital Road, 97201, Portland, OR, USA aut NATIONALLICENCE 700 1- Casey Daniel Research Services, V.A. Medical Center, The Oregon Health Sciences University, 3710 S.W. Veterans Hospital Road, 97201, Portland, OR, USA aut NATIONALLICENCE 700 1- Stallbaumer Regina Research Services, V.A. Medical Center, The Oregon Health Sciences University, 3710 S.W. Veterans Hospital Road, 97201, Portland, OR, USA aut NATIONALLICENCE 700 1- Taylor Barry Research Services, V.A. Medical Center, The Oregon Health Sciences University, 3710 S.W. Veterans Hospital Road, 97201, Portland, OR, USA aut NATIONALLICENCE 773 0- Psychopharmacology Springer-Verlag 106/1(1992-01-01), 45-52 0033-3158 106:1<45 1992 106 213 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer