CNS monoamine levels and motoric behaviors in the hotfoot ataxic mutant.
Mice that were homozygous recessive for the single-gene mutation, hotfoot, showed profound and progressive motor disturbances in an open field after approximately the 4th postnatal week. Studies were undertaken to examine the role of the monoaminergic system in the behavioral and developmental expression of this neurological mutation. Relative to controls, 10-and 30-day-old hotfoot mice demonstrated a significantly attenuated response to the stimulating locomotor effects of amphetamine while adult hotfoot mice were motorically unaffected by amphetamine administration. 30-day-old and adult hotfoot mice also were hypothermic relative to phenotypically normal mice after amphetamine administration. Examination of monoamine levels and turnover revealed that hotfoot mice had significantly greater concentrations of norepinephrine associated with lower turnover in cerebellum and greater levels of serotonin in cerebellum and striatum, relative to phenotypic controls. In addition, mice born and raised by hotfoot dams demonstrated neurochemical alterations regardless of genotype. Both the neurochemical data and the developmental response to the general catecholamine agonist, amphetamine, suggest that the monaminergic neurotransmitter system may be altered as a consequence of the hotfoot mutation.
Draski
L J
LJ
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
Nash
D J
DJ
Gerhardt
G A
GA
D000375:Aging / Q000502:physiology; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001259:Ataxia / Q000235:genetics* / Q000378:metabolism*; D015306:Biogenic Monoamines / Q000378:metabolism*; D001831:Body Temperature; D001835:Body Weight; D002490:Central Nervous System / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D005838:Genotype; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000235:genetics; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009154:Mutation; D018377:Neurotransmitter Agents / Q000378:metabolism
D015306:Biogenic Monoamines; D018377:Neurotransmitter Agents; D000661:Amphetamine