5-HT systems and anxiety: multiple mechanisms in the elevated X-maze

Although much evidence supports the proposal that 5-HT neurones promote anxiety, there is also substantial evidence that the actual situation is more complex. The recent idea that 5-HT neurones, alerted by the forebrain, also function to restrain more primitive brainstem mechanisms has additional explanatory power but neither proposal accounts for the lack of responsiveness of 5-HT neurones to aversive stimulation from the environment. Evidence from the elevated X-maze anxiety model indicates that it is sensitive to multiple anxiety mechanisms which are not fully accounted for by either hypothesis. In addition, findings presented here indicate that open arm preference, risk assessment and overall motility load on separate factors in a factor analysis and that the anxiogenic action of 8-OH-DPAT under control conditions is a selective effect on open arm preference. This anxiogenic effect can be switched to anxiolytic at will by simple changes in experimental conditions. The outcome of 5-HT system manipulations on experimental anxiety may be the result of unstable balance between effects on different brain areas. It is suggested that 5-HT neurones do not carry information about threats in the environment, instead, this information is input locally where it modulates 5-HT release; this released 5-HT can have different consequences in different brain areas.