Stereotypic Progressions in Psychotic Behavior

Dopamine receptor supersensitivity (DARSS) often is invoked as a mechanism possibly underlying disordered thought processes and agitation states in psychiatric disorders. This review is focused on identified means for producing DARSS and associating the role of other monoaminergic systems in modulating DARSS. Dopamine (DA) receptors, experimentally, are prone to become supersensitive and to thus elicit abnormal behaviors when coupled with DA or a receptor agonist. In intact (control) rats repeated DA D 1 agonist treatments fail to sensitize D 1 receptors, while repeated D 2 agonist treatments sensitize D 2 receptors. D 2 RSS is attenuated by a lesion with DSP-4 ( N -(2-chlorethyl)- N -ethyl-2-bromobenzylamine) in early postnatal ontogeny, indicating that noradrenergic nerves have a permissive effect on D 2 DARSS. However, if DSP-4 is co-administered with 5,7-dihydroxytryptamine to destroy serotonin (5-HT) nerves, then D 2 RSS is restored. In rats treated early in postnatal ontogeny with the neurotoxin 6-hydroxydopamine to largely destroy DA innervation of striatum, both repeated D 1 and D 2 agonists sensitize D 1 receptors. 5-HT nerves appear to have a permissive effect on D 1 DARSS, as a 5-HT lesion reduces the otherwise enhanced effect of a D 1 agonist. The series of findings demonstrate that DARSS is able to be produced by repeated agonist treatments, albeit under different circumstances. The involvement of other neuronal phenotypes as modulators of DARSS provides the potential for targeting a variety of sites in the aim to prevent or attenuate DARSS. This therapeutic potential broadens the realm of approaches toward treating psychiatric disorders.