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.
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D003863:Depression / Q000188:drug therapy; D004298:Dopamine / Q000494:pharmacology; D006801:Humans; D008995:Monoamine Oxidase / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000096:biosynthesis / Q000378:metabolism*; D014191:Tranylcypromine / Q000494:pharmacology; D014364:Tryptophan / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000928:Antidepressive Agents; D012701:Serotonin; D014191:Tranylcypromine; D005680:gamma-Aminobutyric Acid; D014364:Tryptophan; D008995:Monoamine Oxidase; D004298:Dopamine