Synchronized overproduction of neurotransmitter receptors in diverse regions of the primate cerebral cortex.

Abstract

A remarkable diversity of neurotrausmitter receptors develops concurrently in disparate areas of the primate cerebral cortex. The density of dopaminergic, adrenergic, serotonergic, cholinergic, and GABAergic receptors (where GABA is r-aminobutyric acid) in rhesus monkey reaches a maximum level between 2 and 4 months of age and then declines gradually to adult levels in all layers of sensory, motor, and association regions. The synchronized development of neurotransmitter receptors in diverse layers and regions of the neocortex occurs parn passu with synaptogenesis, demonstrating unusual coordination of biochemical and structural maturation and supporting the hypothesis that the entire cerebral cortex matures as an integrated network, rather than as a system-by-system cascade.

Developmental Regulation of the Dopamine D1 Receptor in Human Caudate and Putamen

“…Synaptic overproduction and pruning have been envisioned as the primary forces that shape brain maturation during this critical time period. Evidence of postnatal overproduction and subsequent pruning of neurotransmitter receptors in primates can be found in a series of elegant studies in which dopaminergic, serotonergic, noradrenergic and adrenergic systems in macaque cortex have a postnatal increase and eventual decline in receptor density prior to puberty (Rakic et al 1986;Lidow et al 1991;Lidow and Rakic 1992). Studies in rodent striatum likewise provide evidence for overproduction and pruning of D 1 receptors (Teicher et al 1995).…”

Olanzapine Sensitization and Clozapine Tolerance: From Adolescence to Adulthood in the Conditioned Avoidance Response Model

“…For example, adolescents tend to overexpress various neuroreceptors (eg, dopaminergic, adrenergic, serotonergic) followed by pruning to adult levels (an inverted U-shape curve of development). Both dopamine receptors (eg, D 1 , D 2 ) and serotonergic receptors (eg, 5-HT 1A , 5-HT 2A ) that are implicated in the mechanisms of action of antipsychotic drugs are reported to be expressed at higher levels in various brain areas (eg, cerebral cortex, hippocampus, dorsal and ventral striatum, and septum) during adolescence than in adulthood (Lidow et al, 1991;Teicher et al, 1995;Tarazi et al, 1998;Andersen et al, 2000), and antipsychotic exposure alters these neuroreceptors in unique ways not seen in adult animals (Moran-Gates et al, 2006;Choi et al, 2009;Choi et al, 2010). For instance, Moran-Gates et al (2006) found that repeated administration of OLZ (5 mg/kg, once daily) and CLZ (20 mg/kg, twice daily) from P 22 to P 42, all decreased D 1 receptors in dorsolateral frontal and medial prefrontal cortex of adolescent, but not adult rats.…”

Disruption of Rat Forebrain Development by Glucocorticoids: Critical Perinatal Periods for Effects on Neural Cell Acquisition and on Cell Signaling Cascades Mediating Noradrenergic and Cholinergic Neurotransmitter/Neurotrophic Responses

“…We also characterized three neurotransmitter receptor-binding sites, b-adrenoceptor (bAR), a 2 -adrenoceptor (a 2 AR), and m 2 -muscarinic acetylcholine receptor (m 2 AChR). Each receptor has been implicated in the control of neural cell acquisition and differentiation (Duncan et al, 1990;Garofolo et al, 2003;Hodges-Savola et al, 1996;Kreider et al, 2004;Lidow and Rakic, 1995;Slotkin et al, 1988;Zhou et al, 2004) and, like the HC3-binding site, the bAR and a 2 AR are overexpressed in the fetal brain (Kreider et al, 2004;Lidow et al, 1991;Slotkin et al, 1994b;Zahalka et al, 1993a). Notably, glucocorticoids have a direct effect on bAR expression (Davies and Lefkowitz, 1984;Tseng et al, 2002).…”