Altered serotonin and dopamine metabolism in the CNS of serotonin 5-HT(1A) or 5-HT(1B) receptor knockout mice

J Neurochem. 2000 Dec;75(6):2415-26. doi: 10.1046/j.1471-4159.2000.0752415.x.

Abstract

Measurements of serotonin (5-HT), dopamine (DA), and noradrenaline, and of 5-HT and DA metabolites, were obtained by HPLC from 16 brain regions and the spinal cord of 5-HT(1A) or 5-HT(1B) knockout and wild-type mice of the 129/Sv strain. In 5-HT(1A) knockouts, 5-HT concentrations were unchanged throughout, but levels of 5-HT metabolites were higher than those of the wild type in dorsal/medial raphe nuclei, olfactory bulb, substantia nigra, and locus coeruleus. This was taken as an indication of increased 5-HT turnover, reflecting an augmented basal activity of midbrain raphe neurons and consequent increase in their somatodendritic and axon terminal release of 5-HT. It provided a likely explanation for the increased anxious-like behavior observed in 5-HT(1A) knockout mice. Concomitant increases in DA content and/or DA turnover were interpreted as the result of a disinhibition of DA, whereas increases in noradrenaline concentration in some territories of projection of the locus coeruleus could reflect a diminished activity of its neurons. In 5-HT(1B) knockouts, 5-HT concentrations were lower than those of the wild type in nucleus accumbens, locus coeruleus, spinal cord, and probably also several other territories of 5-HT innervation. A decrease in DA, associated with increased DA turnover, was measured in nucleus accumbens. These changes in 5-HT and DA metabolism were consistent with the increased aggressiveness and the supersensitivity to cocaine reported in 5-HT(1B) knockout mice. Thus, markedly different alterations in CNS monoamine metabolism may contribute to the opposite behavioral phenotypes of these two knockouts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / analysis
  • Animals
  • Autoradiography
  • Basal Ganglia / chemistry
  • Basal Ganglia / metabolism
  • Central Nervous System / chemistry
  • Central Nervous System / metabolism*
  • Cerebellum / chemistry
  • Cerebellum / metabolism
  • Cerebral Cortex / chemistry
  • Cerebral Cortex / metabolism
  • Chromatography, High Pressure Liquid
  • Dopamine / analogs & derivatives*
  • Dopamine / analysis
  • Dopamine / metabolism*
  • Female
  • Homovanillic Acid / analysis
  • Hydroxyindoleacetic Acid / analysis
  • Hydroxytryptophol / analysis
  • Hypothalamus / chemistry
  • Hypothalamus / metabolism
  • Male
  • Mesencephalon / chemistry
  • Mesencephalon / metabolism
  • Mice
  • Mice, Knockout
  • Norepinephrine / analysis
  • Olfactory Bulb / chemistry
  • Olfactory Bulb / metabolism
  • Organ Specificity
  • Receptor, Serotonin, 5-HT1B
  • Receptors, Serotonin / deficiency
  • Receptors, Serotonin / genetics*
  • Receptors, Serotonin, 5-HT1
  • Serotonin / analysis
  • Serotonin / metabolism*
  • Spinal Cord / chemistry
  • Spinal Cord / metabolism

Substances

  • Receptor, Serotonin, 5-HT1B
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • 3,4-Dihydroxyphenylacetic Acid
  • Hydroxytryptophol
  • Serotonin
  • Hydroxyindoleacetic Acid
  • 3-methoxytyramine
  • Dopamine
  • Norepinephrine
  • Homovanillic Acid