Significant increase in the aggressive behavior of transgenic mice overexpressing peripheral progastrin peptides

Associated changes in CCK 2 and serotonin receptors in the CNS

Qian Li, Xiaoling Deng, Pomila Singh

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The gastrin precursor peptide, progastrin (PG), is secreted from enteroendocrine cells in the intestine and increased in patients with hypergastrinemia and colorectal cancers. In recent years, we and others have demonstrated an important role of PG peptides in colorectal carcinogenesis, and were surprised to note significant changes in the behaviors of transgenic mice overexpressing PGs. In the present studies, we examined emotional behaviors of transgenic mice overexpressing PG in the intestinal and peripheral circulation. Aggression, locomotor activity and anxiety-like behaviors of the homozygous transgenic (Tg/Tg) mice and the wild-type (WT) littermates were examined by intruder/resident test, open field and elevated plus maze, respectively. A significant increase in the aggression, locomotor activity, and anxiety-like behaviors was detected in the Tg/Tg vs WT mice. As CCK, CCK2 receptors (CCK2R), and 5-HT1A receptors (5-HT 1AR) in the CNS play an important role in these behaviors, possible changes in the expression of CCK and CCK2R and the density of CCK2R and 5-HT1AR were determined by either real-time RT-PCR or autoradiography of ligand binding assays. The results suggest that the expressions of CCK and CCK2R were increased in the hypothalamus, and the density of CCK2R were increased in the hypothalamus and amygdala of Tg/Tg vs WT mice. Similarly, the density of 5-HT1AR was increased in the hypothalamus. Our results suggest that an upregulation of the CCK response system and 5-HT1AR in the hypothalamus of Tg/Tg mice may mediate the alterations in the observed behaviors of these mice.

Original languageEnglish (US)
Pages (from-to)1813-1821
Number of pages9
JournalNeuropsychopharmacology
Volume32
Issue number8
DOIs
StatePublished - Aug 2007

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Cholecystokinin B Receptor
Cholecystokinin Receptors
Transgenic Mice
Serotonin
Hypothalamus
Peptides
Locomotion
Aggression
Anxiety
Enteroendocrine Cells
Receptor, Serotonin, 5-HT1A
Gastrins
Amygdala
Autoradiography
Intestines
Real-Time Polymerase Chain Reaction
Colorectal Neoplasms
Carcinogenesis
Up-Regulation
big gastrin

Keywords

  • 5-HT receptors
  • Aggression
  • Anxiety-like
  • CCK
  • CCK receptors
  • Locomotor activity

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "Significant increase in the aggressive behavior of transgenic mice overexpressing peripheral progastrin peptides: Associated changes in CCK 2 and serotonin receptors in the CNS",
abstract = "The gastrin precursor peptide, progastrin (PG), is secreted from enteroendocrine cells in the intestine and increased in patients with hypergastrinemia and colorectal cancers. In recent years, we and others have demonstrated an important role of PG peptides in colorectal carcinogenesis, and were surprised to note significant changes in the behaviors of transgenic mice overexpressing PGs. In the present studies, we examined emotional behaviors of transgenic mice overexpressing PG in the intestinal and peripheral circulation. Aggression, locomotor activity and anxiety-like behaviors of the homozygous transgenic (Tg/Tg) mice and the wild-type (WT) littermates were examined by intruder/resident test, open field and elevated plus maze, respectively. A significant increase in the aggression, locomotor activity, and anxiety-like behaviors was detected in the Tg/Tg vs WT mice. As CCK, CCK2 receptors (CCK2R), and 5-HT1A receptors (5-HT 1AR) in the CNS play an important role in these behaviors, possible changes in the expression of CCK and CCK2R and the density of CCK2R and 5-HT1AR were determined by either real-time RT-PCR or autoradiography of ligand binding assays. The results suggest that the expressions of CCK and CCK2R were increased in the hypothalamus, and the density of CCK2R were increased in the hypothalamus and amygdala of Tg/Tg vs WT mice. Similarly, the density of 5-HT1AR was increased in the hypothalamus. Our results suggest that an upregulation of the CCK response system and 5-HT1AR in the hypothalamus of Tg/Tg mice may mediate the alterations in the observed behaviors of these mice.",
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T1 - Significant increase in the aggressive behavior of transgenic mice overexpressing peripheral progastrin peptides

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AU - Li, Qian

AU - Deng, Xiaoling

AU - Singh, Pomila

PY - 2007/8

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N2 - The gastrin precursor peptide, progastrin (PG), is secreted from enteroendocrine cells in the intestine and increased in patients with hypergastrinemia and colorectal cancers. In recent years, we and others have demonstrated an important role of PG peptides in colorectal carcinogenesis, and were surprised to note significant changes in the behaviors of transgenic mice overexpressing PGs. In the present studies, we examined emotional behaviors of transgenic mice overexpressing PG in the intestinal and peripheral circulation. Aggression, locomotor activity and anxiety-like behaviors of the homozygous transgenic (Tg/Tg) mice and the wild-type (WT) littermates were examined by intruder/resident test, open field and elevated plus maze, respectively. A significant increase in the aggression, locomotor activity, and anxiety-like behaviors was detected in the Tg/Tg vs WT mice. As CCK, CCK2 receptors (CCK2R), and 5-HT1A receptors (5-HT 1AR) in the CNS play an important role in these behaviors, possible changes in the expression of CCK and CCK2R and the density of CCK2R and 5-HT1AR were determined by either real-time RT-PCR or autoradiography of ligand binding assays. The results suggest that the expressions of CCK and CCK2R were increased in the hypothalamus, and the density of CCK2R were increased in the hypothalamus and amygdala of Tg/Tg vs WT mice. Similarly, the density of 5-HT1AR was increased in the hypothalamus. Our results suggest that an upregulation of the CCK response system and 5-HT1AR in the hypothalamus of Tg/Tg mice may mediate the alterations in the observed behaviors of these mice.

AB - The gastrin precursor peptide, progastrin (PG), is secreted from enteroendocrine cells in the intestine and increased in patients with hypergastrinemia and colorectal cancers. In recent years, we and others have demonstrated an important role of PG peptides in colorectal carcinogenesis, and were surprised to note significant changes in the behaviors of transgenic mice overexpressing PGs. In the present studies, we examined emotional behaviors of transgenic mice overexpressing PG in the intestinal and peripheral circulation. Aggression, locomotor activity and anxiety-like behaviors of the homozygous transgenic (Tg/Tg) mice and the wild-type (WT) littermates were examined by intruder/resident test, open field and elevated plus maze, respectively. A significant increase in the aggression, locomotor activity, and anxiety-like behaviors was detected in the Tg/Tg vs WT mice. As CCK, CCK2 receptors (CCK2R), and 5-HT1A receptors (5-HT 1AR) in the CNS play an important role in these behaviors, possible changes in the expression of CCK and CCK2R and the density of CCK2R and 5-HT1AR were determined by either real-time RT-PCR or autoradiography of ligand binding assays. The results suggest that the expressions of CCK and CCK2R were increased in the hypothalamus, and the density of CCK2R were increased in the hypothalamus and amygdala of Tg/Tg vs WT mice. Similarly, the density of 5-HT1AR was increased in the hypothalamus. Our results suggest that an upregulation of the CCK response system and 5-HT1AR in the hypothalamus of Tg/Tg mice may mediate the alterations in the observed behaviors of these mice.

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