Soderstrom K, Johnson F
Florida State University, Department of Psychology, Tallahassee, FL 32306-1270, USA.
J Pharmacol Exp Ther. 2001 Apr;297(1):189-97.
Zebra finches (Taeniopygia guttata) learn vocal behavior during sensitive developmental periods, similar to the way in which human language is acquired. As adults, they recite the learned song pattern in a stereotyped manner. Previously, we demonstrated that central nervous system-associated cannabinoid receptors (CB1) are expressed in brain regions known to control both juvenile song learning and adult recitation of song. Here we extend these findings by establishing the zebra finch as a behavioral model to study cannabinoid pharmacology, showing that the cannabinoid agonist WIN55212-2 inhibits both adult song production and locomotor activity, effects that are antagonist-reversed. Through radioligand binding assays we investigated the pharmacology of a number of cannabinoid ligands representing all structural classes and established an affinity profile that can be compared with that of other species. To begin to characterize signal transduction mechanisms we isolated cDNA encoding the receptor protein. The zebra finch CB1 receptor (ZFCB1) is highly expressed in brain with amino acid sequence 92% identical to human CB1 receptor. Establishment of a Chinese hamster ovary cell line stably expressing ZFCB1 allowed demonstration that the cannabinoid agonist WIN55212-2 dose dependently and potently inhibits forskolin-stimulated adenylate cyclase activity (IC(50) = 9.0 nM, maximum inhibition = 49% at 100 nM WIN55212-2, reversed by 1 mM SR141716A). Cyclase inhibition indicates that ZFCB1-mediated signal transduction is consistent with that of mammalian CB1 receptors. Overall, cannabinoid inhibition of adult song production and conserved pharmacology render the zebra finch a promising model to investigate cannabinoid effects on learning by juveniles.
斑胸草雀（Taeniopygia guttata）在敏感的发育时期学习发声行为，这与人类语言习得的方式类似。成年后，它们会以刻板的方式背诵所学的歌曲模式。此前，我们证明与中枢神经系统相关的大麻素受体（CB1）在已知控制幼鸟歌曲学习和成年鸟鸣背诵的脑区中表达。在这里，我们通过将斑胸草雀确立为研究大麻素药理学的行为模型来扩展这些发现，表明大麻素激动剂WIN55212-2抑制成年鸟鸣的产生和运动活动，这些作用可被拮抗剂逆转。通过放射性配体结合试验，我们研究了代表所有结构类别的多种大麻素配体的药理学，并建立了一个可以与其他物种进行比较的亲和力图谱。为了开始表征信号转导机制，我们分离了编码受体蛋白的cDNA。斑胸草雀CB1受体（ZFCB1）在脑中高度表达，其氨基酸序列与人类CB1受体有92%的同一性。建立稳定表达ZFCB1的中国仓鼠卵巢细胞系，使得能够证明大麻素激动剂WIN55212-2剂量依赖性地强力抑制福斯高林刺激的腺苷酸环化酶活性（IC(50)=9.0 nM，在100 nM WIN55212-2时最大抑制率为49%，被1 mM SR141716A逆转）。环化酶抑制表明ZFCB1介导的信号转导与哺乳动物CB1受体一致。总体而言，大麻素对成年鸟鸣产生的抑制作用和保守的药理学特性使斑胸草雀成为研究大麻素对幼鸟学习影响的一个有前途的模型。
