Processes regulating the functional activity of brain 5-hydroxytryptamine: results of animal experimentation and their relevance to the understanding and treatment of depression.

Investigation has been made into the processes regulating the function activity of rat brain 5-hydroxytryptamine (5-HT) and the way that drugs used to treat depression act on these processes. Use was made of both biochemical measurements and a behavioural model in which the hyperactivity which follows increased 5-HT synthesis and release was measured as an index of functional activity of the amine. The following mechanisms are suggested to be important in the control of 5-HT function. Presynaptic mechanisms; precursor availability and the transport of tryptophan across the neuronal membrane, intraneuronal metabolism by monoamine oxidase, compartmentation, release and re-uptake. Postsynaptic mechanisms; the sensitivity of the post-synaptic receptor, the role of peptides in altering the size of the post-synaptic response and the action of other neurotransmitters controlling the magnitude of the postsynaptic response. In this regard 5-HT function has been shown to be altered by both dopamine and GABA. The action of anti-depressant drugs on these mechanisms is discussed.