Zebra finch CB1 cannabinoid receptor: pharmacology and in vivo and in vitro effects of activation.

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.