Stereotypic Progressions in Psychotic Behavior

Abstract

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 D₁ agonist treatments fail to sensitize D₁ receptors, while repeated D₂ agonist treatments sensitize D₂ receptors. D₂ 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 D₂ DARSS. However, if DSP-4 is co-administered with 5,7-dihydroxytryptamine to destroy serotonin (5-HT) nerves, then D₂ RSS is restored. In rats treated early in postnatal ontogeny with the neurotoxin 6-hydroxydopamine to largely destroy DA innervation of striatum, both repeated D₁ and D₂ agonists sensitize D₁ receptors. 5-HT nerves appear to have a permissive effect on D₁ DARSS, as a 5-HT lesion reduces the otherwise enhanced effect of a D₁ 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.