There is evidence that antidepressants are able to modify intracellular signalling, as for example, by enhancing the cyclic AMP pathway activation occurring after serotonergic receptor stimulation. It has been hypothesised that G proteins, important signal transducers in the phosphoinositol system, are overactive in depression; they are also potentially important in the mechanism of action of lithium. Several growth factors and neurotrophins are altered in depression, and may be important in neuronal changes seen in depression. Antidepressants also have effects on the expression of these factors. A new cellular model of depression is evolving in which there are felt to be impairments in signalling pathways that regulate neuroplasticity and cell survival (Manji et al., 2001).
Other models of depression have been developed from observations in animals of the effects of certain cytokines on behaviour, and of the effects of some of these cytokines in humans (Kronfol & Remick, 2000).
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