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Stereotypic Progressions in Psychotic Behavior

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Abstract

Dopamine receptor supersensitivity (DARSS) often is invoked as a mechanism possibly underlying disordered thought processes and agitation states in psychiatric disorders. This review is focused on identified means for producing DARSS and associating the role of other monoaminergic systems in modulating DARSS. Dopamine (DA) receptors, experimentally, are prone to become supersensitive and to thus elicit abnormal behaviors when coupled with DA or a receptor agonist. In intact (control) rats repeated DA D1 agonist treatments fail to sensitize D1 receptors, while repeated D2 agonist treatments sensitize D2 receptors. D2 RSS is attenuated by a lesion with DSP-4 (N-(2-chlorethyl)-N-ethyl-2-bromobenzylamine) in early postnatal ontogeny, indicating that noradrenergic nerves have a permissive effect on D2 DARSS. However, if DSP-4 is co-administered with 5,7-dihydroxytryptamine to destroy serotonin (5-HT) nerves, then D2 RSS is restored. In rats treated early in postnatal ontogeny with the neurotoxin 6-hydroxydopamine to largely destroy DA innervation of striatum, both repeated D1 and D2 agonists sensitize D1 receptors. 5-HT nerves appear to have a permissive effect on D1 DARSS, as a 5-HT lesion reduces the otherwise enhanced effect of a D1 agonist. The series of findings demonstrate that DARSS is able to be produced by repeated agonist treatments, albeit under different circumstances. The involvement of other neuronal phenotypes as modulators of DARSS provides the potential for targeting a variety of sites in the aim to prevent or attenuate DARSS. This therapeutic potential broadens the realm of approaches toward treating psychiatric disorders.

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Abbreviations

5-HT:

5-Hydroxytryptamine, serotonin

5,7-DHT:

5,7-Dihydroxytryptamine

7-OH-DPAT:

(±)-2-(dipropylamine)-7-hydroxy-1,2,3,4-tetrahydronaphthalene

6-OHDA:

6-Hydroxydopamine

DA:

Dopamine

DSP-4:

N-(2-chlorethyl)-N-ethyl-2-bromobenzylamine

SCH 23390:

R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine

SKF 38393:

(±)-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol

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Author notes

  1. John P. Kostrzewa

    Present address: Department of Otolaryngology, School of Medicine, University of Alabama, Birmingham, AL, USA

Authors and Affiliations

  1. Department of Pharmacology, Quillen College of Medicine, East Tennessee State University, PO Box 70577, Johnson City, TN, 37614, USA

    Richard M. Kostrzewa, John P. Kostrzewa, Rose Anna Kostrzewa & Florence P. Kostrzewa

  2. Department of Pharmacology, Medical University of Silesia, 41-808, Zabrze, Poland

    Ryszard Brus & Przemyslaw Nowak

Authors
  1. Richard M. Kostrzewa
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  2. John P. Kostrzewa
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  3. Rose Anna Kostrzewa
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  4. Florence P. Kostrzewa
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  5. Ryszard Brus
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  6. Przemyslaw Nowak
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Correspondence to Richard M. Kostrzewa.

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Kostrzewa, R.M., Kostrzewa, J.P., Kostrzewa, R.A. et al. Stereotypic Progressions in Psychotic Behavior. Neurotox Res 19, 243–252 (2011). https://doi.org/10.1007/s12640-010-9192-0

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  • DOI: https://doi.org/10.1007/s12640-010-9192-0

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