Abstract
Neuroleptics are reported to produce their antipsychotic activity and extrapyramidal side effects by blocking dopamine receptors in the mesolimbic system and striatum respectively. We have thus looked at the characteristics of the binding of 3H-spiroperidol to specific binding sites in these two areas of rat brain and the ability of a number of neuroleptics to displace it from these sites. The 3H-spiroperidol binding sites in the striatum and mesolimbic area are different and evidence has been obtained for an involvement of 5-HT receptors, particularly in the latter area. In the striatum the order of activity of neuroleptics in displacing 3H-spiroperidol binding parallels their clinical potency. This is not the case in the mesolimbic system. Also the ratio of activity of a neuroleptic in the two brain areas does not correlate with its ability to produce extrapyramidal disturbance in man. This may be due to the interaction of neuroleptics, particularly in the mesolimbic system, with receptors not involved in the expression of antipsychotic activity.
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