The 5-HT2-type receptor family

Abstract

5-HT 2 -type receptors occur throughout the central nervous system. These receptors exert more subtle effect on the brain as measured in a variety of behavioural paradigms. Furthermore, behavioral effects are not easily attributed to one receptor subtype alone, although this is for a large part due to lack of truly selective agonists and antagonists. It can be expected that a better understanding of the neurobiology of 5-HT 2 -type receptors through development of selective agonists and antagonists may help in disclosing the design of truly selective 5- HT 2 -type receptor agonists and antagonists for CNS purposes. Furthermore, the development of knock-out mice for the 5-HT 2c receptor is likely to be followed closely by other knock-out mouse strains and strains that over-express certain receptors. These animals will stand model for psychiatric disorders, as the behavioral deficits will become more apparent. Needless to say that compensatory mechanisms are likely to occur as the brain is highly plastic and there is redundant control in most, if not all systems. With respect to 5-HT 2b and 5-HT 2c receptors, this is likely, as evidence for their involvement in cell growth and differentiation has already accumulated. Thus, anatomical and functional deficits are likely to arise at the embryonic stage already. This might be one of the underlying factors in the increased vulnerability to seizures in 5- HT 2c knockout mice [89] . In this respect, the development of inducible knockouts may provide additional model systems for acutely developing disorders, which have no 'organic' origin. The onset of receptor deficit or over-expression can be wholly controlled and studied [98] . This type of progress will prove to be important tools for both neurobiological research as well as for the development pharmacotherapy. In this respect a less laborious approach, i.e. antisense infusion into the brain which produces (partial) knockouts, has already produced data on the importance of a variety of receptors.