title: Counteractive effects of antenatal glucocorticoid treatment on D1 receptor modulation of spatial working memory.
abstract: Antenatal exposure to the glucocorticoid dexamethasone dramatically increases the number of mesencephalic dopaminergic neurons in rat offspring. However, the consequences of this expansion in midbrain dopamine (DA) neurons for behavioural processes in adulthood are poorly understood, including working memory that depends on DA transmission in the prefrontal cortex (PFC).
  
  
  
  We therefore investigated the influence of antenatal glucocorticoid treatment (AGT) on the modulation of spatial working memory by a D1receptor agonist and on D1 receptor binding and DA content in the PFC and striatum.
  
  
  
  Pregnant rats received AGT on gestational days 16-19 by adding dexamethasone to their drinking water. Male offspring reared to adulthood were trained on a delayed alternation spatial working memory task and administered the partial D1agonist SKF38393 (0.3-3 mg/kg) by systemic injection. In separate groups of control and AGT animals, D1receptor binding and DA content were measured post-mortem in the PFC and striatum.
  
  
  
  SKF38393 impaired spatial working memory performance in control rats but had no effect in AGT rats. D1binding was significantly reduced in the anterior cingulate cortex, prelimbic cortex, dorsal striatum and ventral pallidum of AGT rats compared with control animals. However, AGT had no significant effect on brain monoamine levels.
  
  
  
  These findings demonstrate that D1receptors in corticostriatal circuitry down-regulate in response to AGT. This compensatory effect in D1receptors may result from increased DA-ergic tone in AGT rats and underlie the resilience of these animals to the disruptive effects of D1receptor activation on spatial working memory.
authors.affiliation: Department of Psychology, University of Cambridge, Downing Street, Cambridge, CB2 3EB, UK.|Behavioural and Clinical Neuroscience Institute, University of Cambridge, Downing Street, Cambridge, CB2 3EB, UK.
authors.forename: Kanwar
authors.initials: K
authors.lastname: Virdee
authors.affiliation: Department of Psychology, University of Cambridge, Downing Street, Cambridge, CB2 3EB, UK.|Behavioural and Clinical Neuroscience Institute, University of Cambridge, Downing Street, Cambridge, CB2 3EB, UK.
authors.forename: Jiska
authors.initials: J
authors.lastname: Kentrop
authors.affiliation: Department of Psychology, University of Cambridge, Downing Street, Cambridge, CB2 3EB, UK.|Behavioural and Clinical Neuroscience Institute, University of Cambridge, Downing Street, Cambridge, CB2 3EB, UK.
authors.forename: Bianca
authors.initials: B
authors.lastname: Jupp
authors.affiliation: Department of Psychology, University of Cambridge, Downing Street, Cambridge, CB2 3EB, UK.
authors.forename: Bethany
authors.initials: B
authors.lastname: Venus
authors.affiliation: Department of Psychology, University of Cambridge, Downing Street, Cambridge, CB2 3EB, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hensman
authors.affiliation: Department of Biomedical Sciences, University of Westminster, New Cavendish Street, London, W1W 6UW, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: McArthur
authors.affiliation: Department of Psychology, University of Cambridge, Downing Street, Cambridge, CB2 3EB, UK.|Behavioural and Clinical Neuroscience Institute, University of Cambridge, Downing Street, Cambridge, CB2 3EB, UK.
authors.forename: James
authors.initials: J
authors.lastname: Wilkinson
authors.affiliation: Department of Psychology, University of Cambridge, Downing Street, Cambridge, CB2 3EB, UK.|Behavioural and Clinical Neuroscience Institute, University of Cambridge, Downing Street, Cambridge, CB2 3EB, UK.
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Robbins
authors.affiliation: Division of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK.
authors.forename: Glenda
authors.initials: G
authors.lastname: Gillies
authors.affiliation: Department of Psychology, University of Cambridge, Downing Street, Cambridge, CB2 3EB, UK. jwd20@cam.ac.uk.|Behavioural and Clinical Neuroscience Institute, University of Cambridge, Downing Street, Cambridge, CB2 3EB, UK. jwd20@cam.ac.uk.|Department of Psychiatry, University of Cambridge, Cambridge, CB2 2QQ, UK. jwd20@cam.ac.uk.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Dalley
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D066187:Basal Forebrain / Q000187:drug effects / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000378:metabolism; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008570:Memory, Short-Term / Q000187:drug effects*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000187:drug effects* / Q000378:metabolism; D065852:Spatial Memory / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D015306:Biogenic Monoamines; D018491:Dopamine Agonists; D005938:Glucocorticoids; D017447:Receptors, Dopamine D1; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D003907:Dexamethasone; D004298:Dopamine
keywords: Dopamine; Dopamine receptors; Memory; Prefrontal cortex; Schizophrenia