α₂-Adrenergic drug effects on brain monoamines, locomotion, and body temperature are largely abolished in mice lacking the α_2A-adrenoceptor subtype

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• 作者：Lä ; hdesmä ; ki ; Janne ; Sallinen ; Jukka ; MacDonald ; Ewen ; Sirvi&ouml ; Jouni ; Scheinin ; Mika
• 关键词：α ; ₂-adrenoceptor subtypes ; Gene targeting ; Neurochemistry ; Presynaptic receptors
• 刊名：Neuropharmacology
• 出版年：2003
• 出版时间：June, 2003
• 年：2003
• 卷：44
• 期：7
• 页码：882-892
• 全文大小：171 K

文摘

α₂-ARs regulate brain monoaminergic function by inhibiting neuronal firing and release of monoamine neurotransmitters, noradrenaline (NA), serotonin (5-HT) and dopamine (DA). Both α_2A- and α_2C-AR inhibit monoamine release in vitro in brain slices, but the in vivo roles of individual α₂-AR subtypes in modulating monoamine metabolism have not been characterised. Metabolism of brain monoamine neurotransmitters, locomotor activity and body temperature were investigated in mice with targeted inactivation of the gene encoding α_2A-AR (α_2A-knockout, α_2A-KO) and wild-type (WT) mice after treatment with the α₂-AR agonist dexmedetomidine and the antagonist atipamezole. Dexmedetomidine caused profound hypothermia (up to 14.7° C mean reduction in rectal temperature) and locomotor inhibition in WT mice, and inhibited the turnover of NA, 5-HT and DA, but increased NA turnover in α_2A-KO mice. α₂-AR agonist-induced hypothermia and locomotor inhibition were attenuated, but not totally abolished, in α_2A-KO mice. These results suggest that α_2A-ARs are principally responsible for the α₂-AR mediated inhibition of brain monoamine metabolism, but other α₂-ARs, possibly α_2C-ARs, are also involved, especially in the striatum. However, secondary effects of the physiological alterations caused by drug administration, especially hypothermia, may have contributed to the observed neurochemical changes in WT mice.