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Altered behavior and alcohol tolerance in transgenic mice lacking MAO A: a comparison with effects of MAO A inhibitor clorgyline.

Authors
  • Popova, N K
  • Vishnivetskaya, G B
  • Ivanova, E A
  • Skrinskaya, J A
  • Seif, I
Type
Published Article
Journal
Pharmacology Biochemistry and Behavior
Publisher
Elsevier
Publication Date
Dec 01, 2000
Volume
67
Issue
4
Pages
719–727
Identifiers
PMID: 11166062
Source
Medline
License
Unknown

Abstract

The influence of deficiency of monoamine oxidase A (MAO A) gene and the lack of enzyme MAO A on the behavior of transgenic mouse strain (Tg8) was studied. It was shown that MAO-A-lacking mice differed from mice of the wild-type strain C3H/HeJ (C3H) by an attenuated acoustic startle response, prepulse inhibition (PPI) was unchanged. In Tg 8 mice, the exploratory nose-poking in the holeboard test as well as exploratory line crossing in the "light-dark" test were decreased. No effect of MAO A deficiency on locomotor activity was found. No alcohol preference or difference between Tg8 and C3H in ethanol consumption in the free-choice test has been found, although an increase in alcohol tolerance has been demonstrated. Ethanol-induced (0.3 g/100 g ip) sleep latency was longer, duration of sleep was shorter and ethanol hypothermia was reduced in MAO-A-lacking mice. Comparison of effects of MAO A knockout with those of irreversible MAO A inhibitor clorgyline (5 and 10 mg/kg ip) on C3H mice showed a similar reducing effect on ethanol-induced sleep, but potentiated ethanol-induced hypothermia. Clorgyline administration provoked a tendency to decrease of exploratory activity in the nose-poking test and decreased the frequency of exploratory rearings in the light-dark test. Clorgyline (5 and 10 mg/kg) did not affect the acoustic startle response, but a dose of 5 mg/kg diminished PPI. Therefore, Tg8 mice exhibited a decreased startle response and exploratory activity and an increased tolerance to ethanol. A similar increase in tolerance to ethanol-induced sleep and a tendency to decrease exploratory behavior were displayed by clorgyline. Other effects on behavior were different, suggesting the influence of long-lasting action of MAO A knockout and the involvement of a compensatory mechanism in Tg8 mice.

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