Dopamine, serotonin and tachykinin in self-injurious behavior

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The neurobiologic basis of self-injurious behavior (SIB) in Lesch-Nyhan syndrome and in other neuropsychiatric conditions remains unclear. The purpose of this review is to summarize recent data concerning SIB induced by the dopamine (DA) uptake inhibitor, GBR-12909 (GBR) and to compare the neurochemical data that have accumulated over the years on SIB in neonatal 6- hydroxydopamine (60HDA) lesioned rats. The DA uptake inhibitor, GBR, upon repeated administration to adult rats elicits SIB that is temporally associated with a reduction of striatal DA (~30%), increased turnover of serotonin and a robust induction of tachykinin transcription resulting in enhanced biosynthesis and presumably release of tachykinins (substance P and neurokinin A). GBR-induced SIB could be blocked by dopaminergic lesions or by D1 or D2 antagonists. Neonatal dopaminergic lesions result in a high degree of DA loss (>90%) and elevated levels of serotonin. In this model, SIB is precipitated by DA agonists via activation of D1 DA receptors which are in turn linked to an induction of tachykinin biosynthesis and release. The data taken together suggest that (a) a substantial reduction of DA accompanied by an increase in serotonin turnover may be essential conditions that are conducive to the occurrence of SIB, and (b) this phase is either superimposed with, or followed by a D1 and/or D2 DA receptor-linked activation of striatonigral tachykinin neurons resulting in enhanced tachykinin biosynthesis and release that may sustain the SIB. Thus, a dynamic interplay between DA, serotonin and tachykinin neuronal systems of the basal ganglia appear to influence the genesis and/or expression of SIB.

Original languageEnglish
Pages (from-to)2367-2375
Number of pages9
JournalLife Sciences
Volume58
Issue number26
DOIs
StatePublished - May 24 1996

Fingerprint

Tachykinins
Self-Injurious Behavior
Dopamine
Serotonin
Biosynthesis
Dopamine Uptake Inhibitors
Dopamine D1 Receptors
Rats
Chemical activation
Neurokinin A
Dopamine D2 Receptors
Oxidopamine
Dopamine Agonists
Transcription
Substance P
Lesch-Nyhan Syndrome
Neurons
Corpus Striatum
Basal Ganglia

Keywords

  • 6-hydroxydopamine
  • D1 receptor
  • D2 receptor
  • dopamine
  • GBR-12909
  • Lesch- Nyhan syndrome
  • neurokinin A
  • self-injurious behavior
  • sensitization
  • serotonin
  • striatum
  • substance P
  • substantia nigra
  • tachykinin

ASJC Scopus subject areas

  • Pharmacology

Cite this

Dopamine, serotonin and tachykinin in self-injurious behavior. / Sivam, Subbiah.

In: Life Sciences, Vol. 58, No. 26, 24.05.1996, p. 2367-2375.

Research output: Contribution to journalArticle

@article{173af9c9bb624e41b72bbf5a06829a09,
title = "Dopamine, serotonin and tachykinin in self-injurious behavior",
abstract = "The neurobiologic basis of self-injurious behavior (SIB) in Lesch-Nyhan syndrome and in other neuropsychiatric conditions remains unclear. The purpose of this review is to summarize recent data concerning SIB induced by the dopamine (DA) uptake inhibitor, GBR-12909 (GBR) and to compare the neurochemical data that have accumulated over the years on SIB in neonatal 6- hydroxydopamine (60HDA) lesioned rats. The DA uptake inhibitor, GBR, upon repeated administration to adult rats elicits SIB that is temporally associated with a reduction of striatal DA (~30{\%}), increased turnover of serotonin and a robust induction of tachykinin transcription resulting in enhanced biosynthesis and presumably release of tachykinins (substance P and neurokinin A). GBR-induced SIB could be blocked by dopaminergic lesions or by D1 or D2 antagonists. Neonatal dopaminergic lesions result in a high degree of DA loss (>90{\%}) and elevated levels of serotonin. In this model, SIB is precipitated by DA agonists via activation of D1 DA receptors which are in turn linked to an induction of tachykinin biosynthesis and release. The data taken together suggest that (a) a substantial reduction of DA accompanied by an increase in serotonin turnover may be essential conditions that are conducive to the occurrence of SIB, and (b) this phase is either superimposed with, or followed by a D1 and/or D2 DA receptor-linked activation of striatonigral tachykinin neurons resulting in enhanced tachykinin biosynthesis and release that may sustain the SIB. Thus, a dynamic interplay between DA, serotonin and tachykinin neuronal systems of the basal ganglia appear to influence the genesis and/or expression of SIB.",
keywords = "6-hydroxydopamine, D1 receptor, D2 receptor, dopamine, GBR-12909, Lesch- Nyhan syndrome, neurokinin A, self-injurious behavior, sensitization, serotonin, striatum, substance P, substantia nigra, tachykinin",
author = "Subbiah Sivam",
year = "1996",
month = "5",
day = "24",
doi = "10.1016/0024-3205(96)00121-X",
language = "English",
volume = "58",
pages = "2367--2375",
journal = "Life Sciences",
issn = "0024-3205",
publisher = "Elsevier Inc.",
number = "26",

}

TY - JOUR

T1 - Dopamine, serotonin and tachykinin in self-injurious behavior

AU - Sivam, Subbiah

PY - 1996/5/24

Y1 - 1996/5/24

N2 - The neurobiologic basis of self-injurious behavior (SIB) in Lesch-Nyhan syndrome and in other neuropsychiatric conditions remains unclear. The purpose of this review is to summarize recent data concerning SIB induced by the dopamine (DA) uptake inhibitor, GBR-12909 (GBR) and to compare the neurochemical data that have accumulated over the years on SIB in neonatal 6- hydroxydopamine (60HDA) lesioned rats. The DA uptake inhibitor, GBR, upon repeated administration to adult rats elicits SIB that is temporally associated with a reduction of striatal DA (~30%), increased turnover of serotonin and a robust induction of tachykinin transcription resulting in enhanced biosynthesis and presumably release of tachykinins (substance P and neurokinin A). GBR-induced SIB could be blocked by dopaminergic lesions or by D1 or D2 antagonists. Neonatal dopaminergic lesions result in a high degree of DA loss (>90%) and elevated levels of serotonin. In this model, SIB is precipitated by DA agonists via activation of D1 DA receptors which are in turn linked to an induction of tachykinin biosynthesis and release. The data taken together suggest that (a) a substantial reduction of DA accompanied by an increase in serotonin turnover may be essential conditions that are conducive to the occurrence of SIB, and (b) this phase is either superimposed with, or followed by a D1 and/or D2 DA receptor-linked activation of striatonigral tachykinin neurons resulting in enhanced tachykinin biosynthesis and release that may sustain the SIB. Thus, a dynamic interplay between DA, serotonin and tachykinin neuronal systems of the basal ganglia appear to influence the genesis and/or expression of SIB.

AB - The neurobiologic basis of self-injurious behavior (SIB) in Lesch-Nyhan syndrome and in other neuropsychiatric conditions remains unclear. The purpose of this review is to summarize recent data concerning SIB induced by the dopamine (DA) uptake inhibitor, GBR-12909 (GBR) and to compare the neurochemical data that have accumulated over the years on SIB in neonatal 6- hydroxydopamine (60HDA) lesioned rats. The DA uptake inhibitor, GBR, upon repeated administration to adult rats elicits SIB that is temporally associated with a reduction of striatal DA (~30%), increased turnover of serotonin and a robust induction of tachykinin transcription resulting in enhanced biosynthesis and presumably release of tachykinins (substance P and neurokinin A). GBR-induced SIB could be blocked by dopaminergic lesions or by D1 or D2 antagonists. Neonatal dopaminergic lesions result in a high degree of DA loss (>90%) and elevated levels of serotonin. In this model, SIB is precipitated by DA agonists via activation of D1 DA receptors which are in turn linked to an induction of tachykinin biosynthesis and release. The data taken together suggest that (a) a substantial reduction of DA accompanied by an increase in serotonin turnover may be essential conditions that are conducive to the occurrence of SIB, and (b) this phase is either superimposed with, or followed by a D1 and/or D2 DA receptor-linked activation of striatonigral tachykinin neurons resulting in enhanced tachykinin biosynthesis and release that may sustain the SIB. Thus, a dynamic interplay between DA, serotonin and tachykinin neuronal systems of the basal ganglia appear to influence the genesis and/or expression of SIB.

KW - 6-hydroxydopamine

KW - D1 receptor

KW - D2 receptor

KW - dopamine

KW - GBR-12909

KW - Lesch- Nyhan syndrome

KW - neurokinin A

KW - self-injurious behavior

KW - sensitization

KW - serotonin

KW - striatum

KW - substance P

KW - substantia nigra

KW - tachykinin

UR - http://www.scopus.com/inward/record.url?scp=0029992395&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029992395&partnerID=8YFLogxK

U2 - 10.1016/0024-3205(96)00121-X

DO - 10.1016/0024-3205(96)00121-X

M3 - Article

C2 - 8691981

AN - SCOPUS:0029992395

VL - 58

SP - 2367

EP - 2375

JO - Life Sciences

JF - Life Sciences

SN - 0024-3205

IS - 26

ER -