Effect of haloperidol and clozapine on the density of "perforated" synapses in caudate, nucleus accumbens, and medial prefrontal cortex

Charles K. Meshul, Aaron Janowsky, Daniel Casey, Regina K. Stallbaumer, Barry Taylor

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

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 This effect was reversed if the animals were withdrawn from the drug for an equivalent period of time.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.

Original languageEnglish (US)
Pages (from-to)45-52
Number of pages8
JournalPsychopharmacology
Volume106
Issue number1
DOIs
StatePublished - Jan 1992

Fingerprint

Caudate Nucleus
Clozapine
Nucleus Accumbens
Haloperidol
Prefrontal Cortex
Synapses
Serotonin 5-HT2 Receptors
Post-Synaptic Density
Behavior Control
Dopaminergic Neurons
Incidence
Dopamine Receptors
Substantia Nigra
Dopamine
Down-Regulation
Membranes
Pharmaceutical Preparations
Tardive Dyskinesia

Keywords

  • Clozapine
  • Electron microscopy
  • Extrapyramidal syndrome
  • Haloperidol
  • Perforated synapses
  • Tardive dyskinesia

ASJC Scopus subject areas

  • Pharmacology

Cite this

Effect of haloperidol and clozapine on the density of "perforated" synapses in caudate, nucleus accumbens, and medial prefrontal cortex. / Meshul, Charles K.; Janowsky, Aaron; Casey, Daniel; Stallbaumer, Regina K.; Taylor, Barry.

In: Psychopharmacology, Vol. 106, No. 1, 01.1992, p. 45-52.

Research output: Contribution to journalArticle

Meshul, Charles K. ; Janowsky, Aaron ; Casey, Daniel ; Stallbaumer, Regina K. ; Taylor, Barry. / Effect of haloperidol and clozapine on the density of "perforated" synapses in caudate, nucleus accumbens, and medial prefrontal cortex. In: Psychopharmacology. 1992 ; Vol. 106, No. 1. pp. 45-52.
@article{217ba9380b8a4ac2b4040d7cce5f08da,
title = "Effect of haloperidol and clozapine on the density of {"}perforated{"} synapses in caudate, nucleus accumbens, and medial prefrontal cortex",
abstract = "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.",
keywords = "Clozapine, Electron microscopy, Extrapyramidal syndrome, Haloperidol, Perforated synapses, Tardive dyskinesia",
author = "Meshul, {Charles K.} and Aaron Janowsky and Daniel Casey and Stallbaumer, {Regina K.} and Barry Taylor",
year = "1992",
month = "1",
doi = "10.1007/BF02253587",
language = "English (US)",
volume = "106",
pages = "45--52",
journal = "Psychopharmacology",
issn = "0033-3158",
publisher = "Springer Verlag",
number = "1",

}

TY - JOUR

T1 - Effect of haloperidol and clozapine on the density of "perforated" synapses in caudate, nucleus accumbens, and medial prefrontal cortex

AU - Meshul, Charles K.

AU - Janowsky, Aaron

AU - Casey, Daniel

AU - Stallbaumer, Regina K.

AU - Taylor, Barry

PY - 1992/1

Y1 - 1992/1

N2 - 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.

AB - 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.

KW - Clozapine

KW - Electron microscopy

KW - Extrapyramidal syndrome

KW - Haloperidol

KW - Perforated synapses

KW - Tardive dyskinesia

UR - http://www.scopus.com/inward/record.url?scp=0026808298&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026808298&partnerID=8YFLogxK

U2 - 10.1007/BF02253587

DO - 10.1007/BF02253587

M3 - Article

C2 - 1531388

AN - SCOPUS:0026808298

VL - 106

SP - 45

EP - 52

JO - Psychopharmacology

JF - Psychopharmacology

SN - 0033-3158

IS - 1

ER -