title: Cocaine exposure prior to pregnancy alters the psychomotor response to cocaine and transcriptional regulation of the dopamine D1 receptor in adult male offspring.
abstract: There is evidence that maternal experience prior to pregnancy can play an important role in behavioral, physiological, and genetic programming of offspring. Likewise, exposure to cocaine in utero can result in marked changes in central nervous system function of offspring. In this study, we examined whether exposure of rat dams to cocaine prior to pregnancy subsequently alters indices of behavior, physiology, and gene expression in offspring. Multiple outcome measures were examined in adult male offspring: (1) behavioral expression of cocaine-induced psychomotor activation; (2) levels of corticosterone in response to immobilization stress; and (3) expression of multiple genes, including dopamine receptor D1 (DRD1) and D2 (DRD2), glucocorticoid receptor (GR), and corticotropin-releasing factor (CRF), in functionally relevant brain regions. Adult Sprague-Dawley females were exposed to cocaine (15-30 mg/kg, i.p.) or saline for 10 days, and were then mated to drug naïve males of the same strain. Separate groups of adult male offspring were tested for their acute psychomotor response to cocaine (0, 15, 30 mg/kg, i.p.), corticosterone responsivity to 20 min of immobilization stress, and expression of multiple genes using quantitative PCR. Offspring of dams exposed to cocaine prior to conception exhibited increased psychomotor sensitivity to cocaine, and upregulated gene expression of DRD1 in the medial prefrontal cortex (mPFC). Neither stress-induced corticosterone levels nor gene expression of GR or CRF genes were altered. These data suggest that cocaine exposure before pregnancy can serve to enhance psychomotor sensitivity to cocaine in offspring, possibly via alterations in dopamine function that include upregulation of the DRD1.
authors.affiliation: Centre for the Neurobiology of Stress, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada; Department of Cell and Systems Biology, University of Toronto, 1265 Military Trail, Toronto, ON M1C 1A4, Canada.
authors.forename: Aya
authors.initials: A
authors.lastname: Sasaki
authors.affiliation: Department of Psychology, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada.
authors.forename: Andrea
authors.initials: A
authors.lastname: Constantinof
authors.affiliation: Department of Cell and Systems Biology, University of Toronto, 1265 Military Trail, Toronto, ON M1C 1A4, Canada.
authors.forename: Pauline
authors.initials: P
authors.lastname: Pan
authors.affiliation: Centre for the Neurobiology of Stress, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada; Department of Psychology, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada.
authors.forename: Dave A
authors.initials: DA
authors.lastname: Kupferschmidt
authors.affiliation: Centre for the Neurobiology of Stress, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada; Department of Cell and Systems Biology, University of Toronto, 1265 Military Trail, Toronto, ON M1C 1A4, Canada.
authors.forename: Patrick O
authors.initials: PO
authors.lastname: McGowan
authors.affiliation: Centre for the Neurobiology of Stress, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada; Department of Psychology, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada; Department of Cell and Systems Biology, University of Toronto, 1265 Military Trail, Toronto, ON M1C 1A4, Canada. Electronic address: erb@utsc.utoronto.ca.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Erb
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D003042:Cocaine / Q000633:toxicity*; D018765:Dopamine Uptake Inhibitors / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D008297:Male; D008425:Maternal Behavior / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000503:physiopathology*; D011596:Psychomotor Disorders / Q000209:etiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology
chemical_list: D018765:Dopamine Uptake Inhibitors; D017447:Receptors, Dopamine D1; D003042:Cocaine
keywords: Dopamine gene expression; HPA stress axis; Maternal cocaine; Preconception; Pregestation; Psychomotor activity