Ethanol-induced behavioral sensitization in adolescent and adult mice

Role of the nNOS gene

Yossef Itzhak, Karen L. Anderson

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: In the brain, nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) has a role in synaptic plasticity. Recent evidence suggests the role of NO in a variety of effects produced by alcohol in the central nervous system. The current study investigated the role of the nNOS gene in the development of behavioral sensitization to ethanol in adolescent and adult mice. Methods: Adolescent and adult wild type (WT; B6;129SF2) and nNOS knockout (KO; B6;129S4-Nos1) mice of both sexes received saline or ethanol (1.5 g/kg; intraperitoneally) for 5 consecutive days, and locomotor activity was recorded daily. The locomotor response to challenge ethanol and saline injections was investigated at various time points following withdrawal from ethanol. Results: Adolescent WT but not nNOS KO mice developed a long-lasting sensitized response to ethanol as well as context-dependent hyperlocomotion (in response to saline) from adolescence through adulthood; sex-dependent differences were not observed. Compared to adolescent WT mice, adult WT males developed a short-term sensitized response to ethanol and context-dependent hyperlocomotion; adult WT females showed only short-term context-dependent hyperlocomotion. Adult nNOS KO males (like their adolescent counterparts) did not develop behavioral sensitization; no significant differences between adult nNOS KO and WT females were observed. Blood ethanol concentrations did not show genotype- or sex-dependent differences. Conclusions: (1) The nNOS gene is required for the development of behavioral sensitization to ethanol in adolescent male and female mice. (2) Adolescent exposure to ethanol results in long-lasting behavioral sensitization through adulthood, while adult exposure to ethanol results in a shorter behavioral sensitization. (3) Sex-dependent differences are observed when ethanol exposure begins in adulthood but not in adolescence. (4) Ethanol-induced behavioral sensitization in adulthood is nNOS-dependent in males but not in females. Taken together, results suggest genotype-, ontogeny-, and sex-dependent differences in the development of behavioral sensitization to ethanol.

Original languageEnglish
Pages (from-to)1839-1848
Number of pages10
JournalAlcoholism: Clinical and Experimental Research
Volume32
Issue number10
DOIs
StatePublished - Oct 1 2008

Fingerprint

Nitric Oxide Synthase Type I
Ethanol
Genes
Sex Characteristics
Nitric Oxide
Genotype
Neuronal Plasticity
Neurology
Locomotion
Plasticity
Brain

Keywords

  • Adolescent
  • Behavioral sensitization
  • Ethanol
  • Neuronal nitric oxide synthase
  • NNOS knockout mice

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health
  • Toxicology

Cite this

Ethanol-induced behavioral sensitization in adolescent and adult mice : Role of the nNOS gene. / Itzhak, Yossef; Anderson, Karen L.

In: Alcoholism: Clinical and Experimental Research, Vol. 32, No. 10, 01.10.2008, p. 1839-1848.

Research output: Contribution to journalArticle

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