5HT drugs in animal models of anxiety.

Abstract

It has been widely accepted that 5HT neurones promote anxiety, in humans as well as in animal models. This could be termed the "classic" hypothesis and it has led to a determined search for drugs which reduce 5HT function, especially agents which have selective actions at 5HT receptor subtypes. However, these novel agents tend to have weak and/or variable effects in animal models and more detailed examination of their actions suggests that not all findings are accounted for by the classic hypothesis. There appear to be circumstances in which increased 5HT activity can reduce anxious behaviour. There is increasing evidence for multiple anxiety mechanisms, which may be able to explain differential patterns of drug effects within and between models. Animal models of anxiety may also detect non-anxiety factors: effects on cognition or on impulsivity could be reflected in some models. This could be important in the light of recent evidence that 5HT-selective reuptake inhibitors are effective in impulsivity disorders. The classic hypothesis of 5HT function in anxiety may be only one part of an increasingly complex story. Unravelling the rest of this story is likely to lead to new insights in our understanding of anxiety and related disorders.