title: Postnatal maternal deprivation and pubertal stress have additive effects on dopamine D2 receptor and CaMKII beta expression in the striatum.
abstract: The goal of this study was to determine whether two stressors commonly used to model aspects of neuropsychiatric disease in rats have an additive effect on striatal dopamine type 2 receptor (D2R) expression, a key player in the etiology of neuropsychiatric disease. Animals subjected to early postnatal stress show alterations in function of the dopaminergic system thought to be mediated by stress-induced glucocorticoid release. Subsequent stress during puberty is known to further impact the dopaminergic system and result in dopaminergic hyperactivity analogous to schizophrenia. We exposed rats to maternal deprivation (MD) during the second postnatal week, a time of active striatal development. A subset of these animals were then subjected to pubertal stress induced by immobilization. Both procedures are know to induce glucocorticoid release. At the conclusion of the MD protocol, we observed upregulation in the expression of D2R and of dopamine- and cAMP-regulated phosphoprotein 32-KD (DARPP-32; PPP1R1B), but not of D1R, calcium/calmodulin-dependent protein kinase II beta (CaMKIIβ), CaMKIIα or neurokinin B (NKB). Animals exposed to pubertal stress showed upregulation in expression of both D2R and CaMKIIβ. Furthermore, rats previously exposed to MD showed a much greater upregulation in CaMKIIβ expression, than animals only exposed to pubertal stress. These results support the two-hit hypothesis, indicating that such stressors have an additive effect. The main targets appear to be the D2R and the CaMKIIβ, the latter being an important member of the DR signalling pathway, both of which are associated with schizophrenia.
authors: Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada. gabriela.novak@alumni.utoronto.ca
authors: Gabriela
authors: G
authors: Novak
authors: Theresa
authors: T
authors: Fan
authors: Brian F
authors: BF
authors: O'Dowd
authors: Susan R
authors: SR
authors: George
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D008297:Male; D008426:Maternal Deprivation; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D017448:Receptors, Dopamine D2; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2