Control of dorsal raphe 5-HT function by multiple 5-HT1 autoreceptors:: parallel purposes or pointless plurality?

The serotonergic cells of the dorsal raphe nucleus innervate much of the forebrain and are thought to be involved in the mechanism of action of antidepressants. Dysfunction of these cells might be involved in the neural mechanisms underlying depression and suicide. The traffic in pathways emanating from the dorsal raphe nucleus is controlled by 5-HT1 autoreceptors. Until recently it was thought that the autoreceptors in the dorsal raphe nucleus were solely of the 5-HT1A subtype. In this article, we discuss evidence that the situation is more complex and that multiple 5-HT1 subtypes govern different aspects of 5-HT function in the dorsal raphe nucleus presenting new therapeutic opportunities.