Multiple serotonin mechanisms in animal models of anxiety: environmental, emotional and cognitive factors.

Responses to serotonergic drugs in animal models of 'anxiety' are reviewed with emphasis on the elevated X-maze. Evidence for the 'classic' hypothesis, that decreasing serotonergic function is anxiolytic and increasing it anxiogenic, is most consistent in models of behavioural inhibition where the stimulus inhibits an approach response (conflict models). However, paradoxical drug effects are also frequent, especially where the aversive stimulus evokes an active response. Both types of drug effect are equally frequent in the elevated X-maze. 'Anxiety' models may detect multiple sites and mechanisms of action of the same drug; this may indicate multiple anxiety-related neurological mechanisms in the brain. However, not all drug effects in 'anxiety' models are necessarily related to anxiety itself. It is possible that cognitive factors may affect stimulus evaluation, and response inhibition by an aversive stimulus may be a special case of a wider role for serotonin in behavioural control. Clinical implications of these observations are considered.