Chronic haloperidol-induced changes in regional dopamine release and metabolism and neurotensin content in rats

R. E. See, A. M. Lynch, M. Aravagiri, Charles Nemeroff, M. J. Owens

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Chronic neuroleptic administration has previously been shown to alter in vivo measures of dopaminergic function and lead to regionally selective increases in neurotensin levels. In the current study, female rats were administered chronic haloperidol for 6 months via subcutaneous silastic implants. After 24 weeks of administration, microdialysis probes were inserted into the lateral caudate putamen and the medial prefrontal cortex. Basal samples were collected prior to infusion of a high K+ concentration (100 mM KCI). Extracellular concentrations of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid were assessed using HPLC. Chronic haloperidol-treated rats showed increased basal dopamine metabolite levels in the caudate putamen and an altered response to the effects of high K+ on 3,4-dihydroxyphenylacetic acid; no significant differences were seen with other analytes in the caudate putamen. Although basal concentrations were not different between groups in the prefrontal cortex, haloperidol-treated rats showed a significant attenuation of response to the effects of high K+ infusion on dopamine metabolite concentrations. Radioimmunoassay measurement of tissue neurotensin content showed highly significant elevations of neurotensin concentrations in the caudate putamen and nucleus accumbens, but not in other brain regions analyzed. These results suggest a confluence of altered dopamine and neurotensin function in the caudate putamen which may be related to motor side effects of haloperidol, whereas changes in prefrontal dopamine function are not associated with altered neurotensin levels.

Original languageEnglish
Pages (from-to)202-209
Number of pages8
JournalBrain Research
Volume704
Issue number2
DOIs
StatePublished - Dec 18 1995
Externally publishedYes

Fingerprint

Neurotensin
Putamen
Haloperidol
Dopamine
3,4-Dihydroxyphenylacetic Acid
Prefrontal Cortex
Homovanillic Acid
Hydroxyindoleacetic Acid
Caudate Nucleus
Microdialysis
Nucleus Accumbens
Antipsychotic Agents
Radioimmunoassay
High Pressure Liquid Chromatography
Brain

Keywords

  • Caudate putamen
  • Cortex
  • Dopamine
  • Haloperidol
  • Microdialysis
  • Neurotensin

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

Cite this

Chronic haloperidol-induced changes in regional dopamine release and metabolism and neurotensin content in rats. / See, R. E.; Lynch, A. M.; Aravagiri, M.; Nemeroff, Charles; Owens, M. J.

In: Brain Research, Vol. 704, No. 2, 18.12.1995, p. 202-209.

Research output: Contribution to journalArticle

See, R. E. ; Lynch, A. M. ; Aravagiri, M. ; Nemeroff, Charles ; Owens, M. J. / Chronic haloperidol-induced changes in regional dopamine release and metabolism and neurotensin content in rats. In: Brain Research. 1995 ; Vol. 704, No. 2. pp. 202-209.
@article{f281f58230c14b568107b9045963fa4b,
title = "Chronic haloperidol-induced changes in regional dopamine release and metabolism and neurotensin content in rats",
abstract = "Chronic neuroleptic administration has previously been shown to alter in vivo measures of dopaminergic function and lead to regionally selective increases in neurotensin levels. In the current study, female rats were administered chronic haloperidol for 6 months via subcutaneous silastic implants. After 24 weeks of administration, microdialysis probes were inserted into the lateral caudate putamen and the medial prefrontal cortex. Basal samples were collected prior to infusion of a high K+ concentration (100 mM KCI). Extracellular concentrations of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid were assessed using HPLC. Chronic haloperidol-treated rats showed increased basal dopamine metabolite levels in the caudate putamen and an altered response to the effects of high K+ on 3,4-dihydroxyphenylacetic acid; no significant differences were seen with other analytes in the caudate putamen. Although basal concentrations were not different between groups in the prefrontal cortex, haloperidol-treated rats showed a significant attenuation of response to the effects of high K+ infusion on dopamine metabolite concentrations. Radioimmunoassay measurement of tissue neurotensin content showed highly significant elevations of neurotensin concentrations in the caudate putamen and nucleus accumbens, but not in other brain regions analyzed. These results suggest a confluence of altered dopamine and neurotensin function in the caudate putamen which may be related to motor side effects of haloperidol, whereas changes in prefrontal dopamine function are not associated with altered neurotensin levels.",
keywords = "Caudate putamen, Cortex, Dopamine, Haloperidol, Microdialysis, Neurotensin",
author = "See, {R. E.} and Lynch, {A. M.} and M. Aravagiri and Charles Nemeroff and Owens, {M. J.}",
year = "1995",
month = "12",
day = "18",
doi = "10.1016/0006-8993(95)01114-5",
language = "English",
volume = "704",
pages = "202--209",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - Chronic haloperidol-induced changes in regional dopamine release and metabolism and neurotensin content in rats

AU - See, R. E.

AU - Lynch, A. M.

AU - Aravagiri, M.

AU - Nemeroff, Charles

AU - Owens, M. J.

PY - 1995/12/18

Y1 - 1995/12/18

N2 - Chronic neuroleptic administration has previously been shown to alter in vivo measures of dopaminergic function and lead to regionally selective increases in neurotensin levels. In the current study, female rats were administered chronic haloperidol for 6 months via subcutaneous silastic implants. After 24 weeks of administration, microdialysis probes were inserted into the lateral caudate putamen and the medial prefrontal cortex. Basal samples were collected prior to infusion of a high K+ concentration (100 mM KCI). Extracellular concentrations of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid were assessed using HPLC. Chronic haloperidol-treated rats showed increased basal dopamine metabolite levels in the caudate putamen and an altered response to the effects of high K+ on 3,4-dihydroxyphenylacetic acid; no significant differences were seen with other analytes in the caudate putamen. Although basal concentrations were not different between groups in the prefrontal cortex, haloperidol-treated rats showed a significant attenuation of response to the effects of high K+ infusion on dopamine metabolite concentrations. Radioimmunoassay measurement of tissue neurotensin content showed highly significant elevations of neurotensin concentrations in the caudate putamen and nucleus accumbens, but not in other brain regions analyzed. These results suggest a confluence of altered dopamine and neurotensin function in the caudate putamen which may be related to motor side effects of haloperidol, whereas changes in prefrontal dopamine function are not associated with altered neurotensin levels.

AB - Chronic neuroleptic administration has previously been shown to alter in vivo measures of dopaminergic function and lead to regionally selective increases in neurotensin levels. In the current study, female rats were administered chronic haloperidol for 6 months via subcutaneous silastic implants. After 24 weeks of administration, microdialysis probes were inserted into the lateral caudate putamen and the medial prefrontal cortex. Basal samples were collected prior to infusion of a high K+ concentration (100 mM KCI). Extracellular concentrations of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid were assessed using HPLC. Chronic haloperidol-treated rats showed increased basal dopamine metabolite levels in the caudate putamen and an altered response to the effects of high K+ on 3,4-dihydroxyphenylacetic acid; no significant differences were seen with other analytes in the caudate putamen. Although basal concentrations were not different between groups in the prefrontal cortex, haloperidol-treated rats showed a significant attenuation of response to the effects of high K+ infusion on dopamine metabolite concentrations. Radioimmunoassay measurement of tissue neurotensin content showed highly significant elevations of neurotensin concentrations in the caudate putamen and nucleus accumbens, but not in other brain regions analyzed. These results suggest a confluence of altered dopamine and neurotensin function in the caudate putamen which may be related to motor side effects of haloperidol, whereas changes in prefrontal dopamine function are not associated with altered neurotensin levels.

KW - Caudate putamen

KW - Cortex

KW - Dopamine

KW - Haloperidol

KW - Microdialysis

KW - Neurotensin

UR - http://www.scopus.com/inward/record.url?scp=0029589338&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029589338&partnerID=8YFLogxK

U2 - 10.1016/0006-8993(95)01114-5

DO - 10.1016/0006-8993(95)01114-5

M3 - Article

C2 - 8788915

AN - SCOPUS:0029589338

VL - 704

SP - 202

EP - 209

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 2

ER -