Dopamine receptor supersensitivity: Development, mechanisms, presentation, and clinical applicability

Abstract

The process of receptor supersensitivity (RSS) has a long history and is an epiphenomenon of neuronal denervation. Dopamine (DA) RSS (DARSS) similarly occurs after DA denervation, and this process is invoked in neuropsychiatric and neurodegenerative disorders. From studies largely over the past 25 years, much has been learned regarding DARSS. For example, overt D1 DARSS occurs after perinatal destruction of nigrostriatal DA fibers. However, following perinatal destruction of DA innervation, the most-prominent behavioral effects of a D1 agonist are observed after a series of D1 agonist treatments--a process known as priming of D1 DA receptors. Moreover, perinatal lesioning of DA fibers produces prominent serotonin (5-HT) RSS, and in fact 5-HT RSS appears to modulate D1 DA RSS. In rodents, receptor supersensitization by these means appears to be irreversible. In contrast to the observed D1 DARSS, D2 DARSS apparently does not occur after perinatal DA denervation. Also, while repeated D1 agonist treatment of intact rats has no observable effect, repeated D2 agonist treatments, during or after the ontogenetic phase, produces prominent life-long D2 RSS. The process may have an association with substance abuse. Therefore, production of D1 and D2 DARSS occurs by different means and under different circumstances, and in association with perhaps different neuronal phenotypes, and with greater incidence in either intact (D2) or DA-lesioned counterparts (D1). The physiological consequence of RSS are multiple.

Staging Neurological Disorders: Expressions of Cognitive and Motor Disorder

“…As described previously (Kostrzewa et al 2008), the process of receptor supersensitivity (RSS) has a long history and is an epiphenomenon of denervation with DARSS being a process that is ideally suitable for examining pathophysiology in both neuropsychiatric and neurodegenerative disorders. Thus, the treatment of stereotypic progression, i.e., motor dyskinetic progression, in association with DARSS, by R.M.…”

Modeling Tardive Dyskinesia: Predictive 5-HT2C Receptor Antagonist Treatment

“…D 1 receptor sensitization was unaccompanied by a change in the B max (i.e., number) and K d (i.e., affinity) of D 1 receptors, and there was no increase in the expression of high-affinity D 1 receptors in neostriatum of those rats with enhancement of VCMs (Gong et al 1994). Clearly, however, D 1 receptor supersensitivity was manifest in 6-OHDA-lesioned rats in relation to VCM induction (Kostrzewa 1995;Kostrzewa et al 1998Kostrzewa et al , 1999Kostrzewa et al , 2003Kostrzewa et al , 2008a.…”

Effects of bariatric surgery on the central nervous system and eating behavior in humans: a systematic review on the neuroimaging studies

“…Dunn et al 13 and Steele et al 8 used variations in the expression of D2 receptors in different brain regions as a parameter for the assessment of dopaminergic function. Theories on the causes of variances of the rate of D2 receptors are based on adaptive phenomena inherent to neurotransmitter-receptor interactions well described in the literature, namely, D2-hypersensitisation (or upregulation) and D2-desensitization (or down-regulation) 21 . Hypersensitisation and desensitization occur when there is a need to adjust the input between a neurotransmitter and its receptor 21 whenever there is fluctuation in the concentration of the neurotransmitter.…”

“…Theories on the causes of variances of the rate of D2 receptors are based on adaptive phenomena inherent to neurotransmitter-receptor interactions well described in the literature, namely, D2-hypersensitisation (or upregulation) and D2-desensitization (or down-regulation) 21 . Hypersensitisation and desensitization occur when there is a need to adjust the input between a neurotransmitter and its receptor 21 whenever there is fluctuation in the concentration of the neurotransmitter. Thus, a hypersensitisation follows a decrease of the availability of dopamine on the synaptic cleft and a desensitization of such molecular structures follows a local increase of dopamine.…”