SK3 K+ channel-deficient mice have enhanced dopamine and serotonin release and altered emotional behaviors

J. P R Jacobsen, P. Weikop, H. H. Hansen, J. D. Mikkelsen, J. P. Redrobe, D. Holst, C. T. Bond, John Adelman, P. Christophersen, N. R. Mirza

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

SK3 K+ channels influence neuronal excitability and are present in 5-hydroxytryptamine (5-HT) and dopamine (DA) nuclei in the brain stem. We therefore hypothesized that SK3 channels affect 5-HT and DA neurotransmission and associated behaviors. To explore this, we used doxycycline-induced conditional SK3-deficient (T/T) mice. In microdialysis, T/T mice had elevated baseline levels of striatal extracellular DA and the metabolites dihydroxyphenylacetic acid and homovanillic acid. While baseline hippocampal extracellular 5-HT was unchanged in T/T mice, the 5-HT response to the 5-HT transporter inhibitor citalopram was enhanced. Furthermore, baseline levels of the 5-HT metabolite 5-hydroxyindoleacetic acid were elevated in T/T mice. T/T mice performed equally to wild type (WT) in most sensory and motor tests, indicating that SK3 deficiency does not lead to gross impairments. In the forced swim and tail suspension tests, the T/T mice displayed reduced immobility compared with WT, indicative of an antidepressant-like phenotype. Female T/T mice were more anxious in the zero maze. In contrast, anxiety-like behaviors in the open-field and four-plate tests were unchanged in T/T mice of both sexes. Home cage diurnal activity was also unchanged in T/T mice. However, SK3 deficiency had a complex effect on activity responses to novelty: T/T mice showed decreased, increased or unchanged activity responses to novelty, depending on sex and context. In summary, we report that SK3 deficiency leads to enhanced DA and 5-HT neurotransmission accompanied by distinct alterations in emotional behaviors.

Original languageEnglish (US)
Pages (from-to)836-848
Number of pages13
JournalGenes, Brain and Behavior
Volume7
Issue number8
DOIs
StatePublished - Nov 2008

Fingerprint

Dopamine
Serotonin
Synaptic Transmission
Hindlimb Suspension
Corpus Striatum
Homovanillic Acid
Citalopram
Hydroxyindoleacetic Acid
Doxycycline
Microdialysis
Antidepressive Agents
Brain Stem
Anxiety
Phenotype
Acids

Keywords

  • Antidepressant-like
  • Anxiety
  • Depression
  • Doxycycline
  • Locomotor

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Genetics
  • Neurology

Cite this

Jacobsen, J. P. R., Weikop, P., Hansen, H. H., Mikkelsen, J. D., Redrobe, J. P., Holst, D., ... Mirza, N. R. (2008). SK3 K+ channel-deficient mice have enhanced dopamine and serotonin release and altered emotional behaviors. Genes, Brain and Behavior, 7(8), 836-848. https://doi.org/10.1111/j.1601-183X.2008.00416.x

SK3 K+ channel-deficient mice have enhanced dopamine and serotonin release and altered emotional behaviors. / Jacobsen, J. P R; Weikop, P.; Hansen, H. H.; Mikkelsen, J. D.; Redrobe, J. P.; Holst, D.; Bond, C. T.; Adelman, John; Christophersen, P.; Mirza, N. R.

In: Genes, Brain and Behavior, Vol. 7, No. 8, 11.2008, p. 836-848.

Research output: Contribution to journalArticle

Jacobsen, JPR, Weikop, P, Hansen, HH, Mikkelsen, JD, Redrobe, JP, Holst, D, Bond, CT, Adelman, J, Christophersen, P & Mirza, NR 2008, 'SK3 K+ channel-deficient mice have enhanced dopamine and serotonin release and altered emotional behaviors', Genes, Brain and Behavior, vol. 7, no. 8, pp. 836-848. https://doi.org/10.1111/j.1601-183X.2008.00416.x
Jacobsen, J. P R ; Weikop, P. ; Hansen, H. H. ; Mikkelsen, J. D. ; Redrobe, J. P. ; Holst, D. ; Bond, C. T. ; Adelman, John ; Christophersen, P. ; Mirza, N. R. / SK3 K+ channel-deficient mice have enhanced dopamine and serotonin release and altered emotional behaviors. In: Genes, Brain and Behavior. 2008 ; Vol. 7, No. 8. pp. 836-848.
@article{52ad996262644b29bfb318efae96d8f2,
title = "SK3 K+ channel-deficient mice have enhanced dopamine and serotonin release and altered emotional behaviors",
abstract = "SK3 K+ channels influence neuronal excitability and are present in 5-hydroxytryptamine (5-HT) and dopamine (DA) nuclei in the brain stem. We therefore hypothesized that SK3 channels affect 5-HT and DA neurotransmission and associated behaviors. To explore this, we used doxycycline-induced conditional SK3-deficient (T/T) mice. In microdialysis, T/T mice had elevated baseline levels of striatal extracellular DA and the metabolites dihydroxyphenylacetic acid and homovanillic acid. While baseline hippocampal extracellular 5-HT was unchanged in T/T mice, the 5-HT response to the 5-HT transporter inhibitor citalopram was enhanced. Furthermore, baseline levels of the 5-HT metabolite 5-hydroxyindoleacetic acid were elevated in T/T mice. T/T mice performed equally to wild type (WT) in most sensory and motor tests, indicating that SK3 deficiency does not lead to gross impairments. In the forced swim and tail suspension tests, the T/T mice displayed reduced immobility compared with WT, indicative of an antidepressant-like phenotype. Female T/T mice were more anxious in the zero maze. In contrast, anxiety-like behaviors in the open-field and four-plate tests were unchanged in T/T mice of both sexes. Home cage diurnal activity was also unchanged in T/T mice. However, SK3 deficiency had a complex effect on activity responses to novelty: T/T mice showed decreased, increased or unchanged activity responses to novelty, depending on sex and context. In summary, we report that SK3 deficiency leads to enhanced DA and 5-HT neurotransmission accompanied by distinct alterations in emotional behaviors.",
keywords = "Antidepressant-like, Anxiety, Depression, Doxycycline, Locomotor",
author = "Jacobsen, {J. P R} and P. Weikop and Hansen, {H. H.} and Mikkelsen, {J. D.} and Redrobe, {J. P.} and D. Holst and Bond, {C. T.} and John Adelman and P. Christophersen and Mirza, {N. R.}",
year = "2008",
month = "11",
doi = "10.1111/j.1601-183X.2008.00416.x",
language = "English (US)",
volume = "7",
pages = "836--848",
journal = "Genes, Brain and Behavior",
issn = "1601-1848",
publisher = "Wiley-Blackwell",
number = "8",

}

TY - JOUR

T1 - SK3 K+ channel-deficient mice have enhanced dopamine and serotonin release and altered emotional behaviors

AU - Jacobsen, J. P R

AU - Weikop, P.

AU - Hansen, H. H.

AU - Mikkelsen, J. D.

AU - Redrobe, J. P.

AU - Holst, D.

AU - Bond, C. T.

AU - Adelman, John

AU - Christophersen, P.

AU - Mirza, N. R.

PY - 2008/11

Y1 - 2008/11

N2 - SK3 K+ channels influence neuronal excitability and are present in 5-hydroxytryptamine (5-HT) and dopamine (DA) nuclei in the brain stem. We therefore hypothesized that SK3 channels affect 5-HT and DA neurotransmission and associated behaviors. To explore this, we used doxycycline-induced conditional SK3-deficient (T/T) mice. In microdialysis, T/T mice had elevated baseline levels of striatal extracellular DA and the metabolites dihydroxyphenylacetic acid and homovanillic acid. While baseline hippocampal extracellular 5-HT was unchanged in T/T mice, the 5-HT response to the 5-HT transporter inhibitor citalopram was enhanced. Furthermore, baseline levels of the 5-HT metabolite 5-hydroxyindoleacetic acid were elevated in T/T mice. T/T mice performed equally to wild type (WT) in most sensory and motor tests, indicating that SK3 deficiency does not lead to gross impairments. In the forced swim and tail suspension tests, the T/T mice displayed reduced immobility compared with WT, indicative of an antidepressant-like phenotype. Female T/T mice were more anxious in the zero maze. In contrast, anxiety-like behaviors in the open-field and four-plate tests were unchanged in T/T mice of both sexes. Home cage diurnal activity was also unchanged in T/T mice. However, SK3 deficiency had a complex effect on activity responses to novelty: T/T mice showed decreased, increased or unchanged activity responses to novelty, depending on sex and context. In summary, we report that SK3 deficiency leads to enhanced DA and 5-HT neurotransmission accompanied by distinct alterations in emotional behaviors.

AB - SK3 K+ channels influence neuronal excitability and are present in 5-hydroxytryptamine (5-HT) and dopamine (DA) nuclei in the brain stem. We therefore hypothesized that SK3 channels affect 5-HT and DA neurotransmission and associated behaviors. To explore this, we used doxycycline-induced conditional SK3-deficient (T/T) mice. In microdialysis, T/T mice had elevated baseline levels of striatal extracellular DA and the metabolites dihydroxyphenylacetic acid and homovanillic acid. While baseline hippocampal extracellular 5-HT was unchanged in T/T mice, the 5-HT response to the 5-HT transporter inhibitor citalopram was enhanced. Furthermore, baseline levels of the 5-HT metabolite 5-hydroxyindoleacetic acid were elevated in T/T mice. T/T mice performed equally to wild type (WT) in most sensory and motor tests, indicating that SK3 deficiency does not lead to gross impairments. In the forced swim and tail suspension tests, the T/T mice displayed reduced immobility compared with WT, indicative of an antidepressant-like phenotype. Female T/T mice were more anxious in the zero maze. In contrast, anxiety-like behaviors in the open-field and four-plate tests were unchanged in T/T mice of both sexes. Home cage diurnal activity was also unchanged in T/T mice. However, SK3 deficiency had a complex effect on activity responses to novelty: T/T mice showed decreased, increased or unchanged activity responses to novelty, depending on sex and context. In summary, we report that SK3 deficiency leads to enhanced DA and 5-HT neurotransmission accompanied by distinct alterations in emotional behaviors.

KW - Antidepressant-like

KW - Anxiety

KW - Depression

KW - Doxycycline

KW - Locomotor

UR - http://www.scopus.com/inward/record.url?scp=56749169241&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=56749169241&partnerID=8YFLogxK

U2 - 10.1111/j.1601-183X.2008.00416.x

DO - 10.1111/j.1601-183X.2008.00416.x

M3 - Article

C2 - 18616612

AN - SCOPUS:56749169241

VL - 7

SP - 836

EP - 848

JO - Genes, Brain and Behavior

JF - Genes, Brain and Behavior

SN - 1601-1848

IS - 8

ER -