title: Early postnatal experience and DRD2 genotype affect dopamine receptor expression in the rat ventral striatum.
abstract: Dopamine systems can be altered by experiences such as early life adversity. The intensity of these effects seems to vary as a function of interactions between genetic and environmental influences. In a series of experiments we have investigated the effects of genetic variants and early life adversity on several biobehavioral outcomes. Here we investigated the presence of single nucleotide polymorphisms (SNPs) in the gene coding for dopamine D2 receptors (DRD2) and the interaction between these variants with early life adversity on the expression of D2 receptors in the striatum. Time-mated pregnant female rats underwent restraint stress (gestational days 10-21) or were left undisturbed. Following parturition rat pups were maternally reared (MR) or artificially reared (AR). Subsequent to adult behavioral testing, rats were genotyped and their brains were processed (autoradiography) for D2 receptor expression. We found three variants in the DRD2 gene and these variants interacted with early adversity to affect D2 receptor expression in the nucleus accumbens. Specifically, artificially reared rats with AG DRD2 variant showed significantly higher D2 expression compared to mother reared rats with the AG DRD2 variant as well as the artificially reared rats with a GG DRD2 variant. These findings show that adult D2 expression is significantly influenced by the interaction of DRD2 SNPs and early developmental factors. These finding may explain why there are significant individual differences in the impact of early life adversity on dopamine-dependent processes and disorder vulnerabilities.
authors.affiliation: Department of Psychology, University of Toronto Mississauga, Canada. vlovic@umich.edu
authors.forename: Vedran
authors.initials: V
authors.lastname: Lovic
authors.forename: Hiwote
authors.initials: H
authors.lastname: Belay
authors.forename: Claire-Dominique
authors.initials: CD
authors.lastname: Walker
authors.forename: Christie L
authors.initials: CL
authors.lastname: Burton
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Meaney
authors.forename: Marla
authors.initials: M
authors.lastname: Sokolowski
authors.forename: Alison S
authors.initials: AS
authors.lastname: Fleming
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001479:Basal Ganglia / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D001549:Benzamides / Q000493:pharmacokinetics; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics*; D005838:Genotype; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology / Q000503:physiopathology; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000235:genetics / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D017366:Serotonin Receptor Agonists; D013312:Stress, Physiological / Q000502:physiology; D014316:Tritium / Q000493:pharmacokinetics
chemical_list: D001549:Benzamides; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D017366:Serotonin Receptor Agonists; D014316:Tritium; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C030265:nemonapride