Long-term treatment with the antioxidant drug EGb 761 at senescence restored some neurobehavioral effects of chronic ultramild stress exposure seen in young mice

Neurobiol Aging. 2004 Sep;25(8):1067-83. doi: 10.1016/j.neurobiolaging.2003.10.013.

Abstract

In this study, we compared the effects of chronic ultramild stress (CUMS) exposure on decision-making behavior in a validated test, and on the stress responsive serotoninergic and dopaminergic systems in four age groups of B6D2F1 female mice (5-6, 11-12, 17-18 and 23-24 months old). The levels of serotonin (5-HT) and its metabolite 5-hydroxyindolacetic acid (5-HIAA) were measured in the brain stem, the cortex, the striatum and the hippocampus; the levels of dopamine (DA) and its metabolite dihydroxyphenylacetic acid (DOPAC) were measured in the brain stem and the striatum. The influence of a long-term treatment with the extract of Ginkgo biloba leaves EGb 761 (Tanakan) on age- and stress-related changes was also investigated in the two oldest age groups. In the absence of drug treatment, middle-age mice were the least efficient in making a decision, and senescent mice exhibited reduced levels of both 5-HT and DA and their metabolites in all the brain areas examined. CUMS facilitated evaluation and choice behavior in all age groups, but induced age-dependent reduction of hesitation, acceleration of information processing and reduction in serotoninergic neurotransmission. In senescent mice, EGb 761 reduced the impact of stress on evaluation and hesitation, and restored some stress-related neurobehavioral changes that were only seen in young mice, i.e. acceleration of information processing and reduction in brain 5-HIAA levels. Restoration of some plasticity of the serotoninergic systems might contribute to the stress alleviating influence of EGb 761 in old age.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Aging / drug effects
  • Aging / metabolism
  • Aging / psychology*
  • Animals
  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Brain / drug effects
  • Brain / metabolism
  • Brain / physiopathology
  • Brain Chemistry / drug effects
  • Brain Chemistry / physiology
  • Chronic Disease / drug therapy
  • Chronic Disease / psychology
  • Cognition Disorders / drug therapy
  • Cognition Disorders / metabolism*
  • Cognition Disorders / physiopathology
  • Decision Making / drug effects
  • Decision Making / physiology*
  • Dopamine / metabolism
  • Drug Administration Schedule
  • Female
  • Ginkgo biloba
  • Hydroxyindoleacetic Acid / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology
  • Nootropic Agents / pharmacology*
  • Nootropic Agents / therapeutic use
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Recovery of Function / drug effects
  • Recovery of Function / physiology
  • Serotonin / metabolism
  • Stress, Psychological / drug therapy
  • Stress, Psychological / metabolism*
  • Stress, Psychological / physiopathology
  • Treatment Outcome

Substances

  • Antioxidants
  • Nootropic Agents
  • Plant Extracts
  • 3,4-Dihydroxyphenylacetic Acid
  • Ginkgo biloba extract
  • Serotonin
  • Hydroxyindoleacetic Acid
  • Dopamine