Behavioral and neurochemical characterization of alpha(2A)-adrenergic receptor knockout mice.
Genetic manipulation of mice now provides new tools to evaluate the biological functions of the alpha(2)-adrenergic receptor (alpha(2)-AR) subtypes (alpha(2A), alpha(2B), and alpha(2C)). To investigate the role of the alpha(2A)-AR in the modulation of mouse primary behavioral characteristics and brain neurochemistry, mice with targeted inactivation of the gene for the alpha(2A)-AR were compared with wild-type C57BL/6 control animals. First, a comprehensive behavioral screen was employed to provide a detailed characterization of basic neurologic functions. Thereafter, the mice were analyzed in three models of anxiety, i.e. the elevated-plus maze test, the marble burying test and the open field test. The diurnal activity pattern of the mice was assessed in a 24-h locomotor activity test. Furthermore, receptor autoradiography of the brain was performed using the subtype-non-selective alpha(2)-AR antagonist radioligand [(3)H]RS-79948-197. Lack of the alpha(2A)-AR was associated with alterations in autonomic functions, including increased heart rate and piloerection. The mutant mice also exhibited impaired motor coordination skills, increased anxiety-like behavior and an abnormal diurnal activity pattern. In addition, neurochemical analysis of monoamine neurotransmitters revealed a considerable increase in brain norepinephrine turnover in mice lacking alpha(2A)-AR. Our results provide further support for the crucial role of the alpha(2A)-AR in modulating brain noradrenergic neurotransmission and many aspects of mouse behavior and physiology.
Department of Pharmacology and Clinical Pharmacology, University of Turku, Itäinen Pitkäkatu 4, FIN-20520, Turku, Finland.
J
J
Lähdesmäki
J
J
Sallinen
E
E
MacDonald
B K
BK
Kobilka
V
V
Fagerholm
M
M
Scheinin
D000818:Animals; D001345:Autoradiography; D001522:Behavior, Animal / Q000502:physiology*; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D009043:Motor Activity / Q000502:physiology; D011942:Receptors, Adrenergic, alpha / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
D015306:Biogenic Monoamines; D011942:Receptors, Adrenergic, alpha