Altered behavior and alcohol tolerance in transgenic mice lacking MAO A: a comparison with effects of MAO A inhibitor clorgyline.
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.
Popova
N K
NK
Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Lavrentieva 10, 630090 Novosibirsk 90, Russia. npopova@bionet.nsc.ru
Vishnivetskaya
G B
GB
Ivanova
E A
EA
Skrinskaya
J A
JA
Seif
I
I
D000428:Alcohol Drinking / Q000235:genetics; D000818:Animals; D001007:Anxiety / Q000235:genetics; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003010:Clorgyline / Q000494:pharmacology*; D004361:Drug Tolerance / Q000235:genetics*; D000431:Ethanol / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology*; D007035:Hypothermia / Q000139:chemically induced / Q000235:genetics; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D008995:Monoamine Oxidase / Q000172:deficiency / Q000235:genetics*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics*; D013216:Reflex, Startle / Q000187:drug effects / Q000235:genetics*; D012890:Sleep / Q000187:drug effects / Q000235:genetics*
D002492:Central Nervous System Depressants; D008996:Monoamine Oxidase Inhibitors; D000431:Ethanol; D008995:Monoamine Oxidase; D003010:Clorgyline