内分泌学
内科学
安非他明
兴奋剂
血清素
刺激
生物
纹状体
多巴胺
受体
医学
作者
Jukka Sallinen,Antti Haapalinna,Timo Viitamaa,Brian K. Kobilka,Mika Scheinin
出处
期刊:Neuroscience
[Elsevier]
日期:1998-06-01
卷期号:86 (3): 959-965
被引量:77
标识
DOI:10.1016/s0306-4522(98)00100-6
摘要
Three human and mouse genes encoding alpha2-adrenoceptor subtypes (alpha2A, alpha2B, and alpha2C) have been cloned. The alpha2C-adrenoceptor is the most abundant alpha2-adrenoceptor subtype in the striatum and modulates metabolism of both dopamine and serotonin. To investigate the possible involvement of the alpha2C-adrenoceptor subtype in behaviours regulated by dopamine and serotonin, two strains of genetically-engineered mice were examined. One had a targeted inactivation of the alpha2C-adrenoceptor gene, and the other had tissue-specific over-expression of alpha2C-adrenoceptors. The locomotor activity of the mice was evaluated after stimulation with D-amphetamine, and the behavioural serotonin syndrome and head twitches were investigated after L-5-hydroxytryptophan treatment. In addition, the effects of D-amphetamine and L-5-hydroxytryptophan were studied after pretreatment with dexmedetomidine, a subtype-nonselective alpha2-adrenoceptor agonist. The lack of alpha2C-adrenoceptor expression increased and the over-expression of alpha2C-adrenoceptors decreased the response to D-amphetamine stimulation. The effect of alpha2C-adrenoceptor gene inactivation was more prominent in D-amphetamine-treated males than in females. Dexmedetomidine inhibited D-amphetamine-induced hyperlocomotion and the L-5-hydroxytryptophan-induced serotonin syndrome, but the inhibition was attenuated in mice lacking alpha2C-adrenoceptors. However, the head twitches induced by L-5-hydroxytryptophan were effectively inhibited by dexmedetomidine in all studied mice, which suggests that alpha2A-adrenoceptors mediate the inhibition of the head twitch response. The results lend further support to the proposed existence of functionally distinct alpha2-adrenoceptor subtypes that can serve as new and specific therapeutic targets in various neuropsychiatric diseases.
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