title: Abnormal synaptic plasticity in basolateral amygdala may account for hyperactivity and attention-deficit in male rat exposed perinatally to low-dose bisphenol-A.
abstract: If the pregnant and lactating female rats are exposed to environmental levels of bisphenol-A (BPA), their male offspring will display hyperactivity and attention-deficit. In patients with attention-deficit/hyperactivity disorder (ADHD), the size of the amygdala is reported to be reduced. This study examined functional alterations in the basolateral amygdala (BLA) of the postnatal 28-day-old male offspring exposed perinatally to BPA (BPA-rats). We specifically focused on the synaptic properties of GABAergic/dopaminergic systems in the BLA. A single electrical stimulation of the capsule fibers evoked multispike responses with an enhanced primary population spikes (1st-PS) in the BPA-rats. A single train of high-frequency stimulation of the fibers induced NMDA receptor (NMDAR) dependent long-term potentiation (LTP) in BPA-rats, but not in control rats. Also, paired-pulse inhibition (PPI, GABA-dependent) in control rats was reversed to paired-pulse facilitation (PPF) in BPA-rats. Perfusion of slices obtained from BPA-rats with the GABA(A) receptor (GABA(A)R) agonist muscimol blocked the multispike responses and LTP, and recovered PPI. By contrast, the dopamine D1 receptor antagonist SCH23390 abolished LTP and attenuated the increased amplitude of 1st-PS in BPA-rats. Conversely, blockade of GABA(A)R by bicuculline could produce the multispike responses and PPF in BLA in control rats. Furthermore, in BLA the infusion of SCH23390, muscimol or the NMDAR blocker MK801 ameliorated the hyperactivity and improved the deficits in attention. These findings suggest that the perinatal exposure to BPA causes GABAergic disinhibition and dopaminergic enhancement, leading to an abnormal cortical-BLA synaptic transmission and plasticity, which may be responsible for the hyperactivity and attention-deficit in BPA-rats. This article is part of a Special Issue entitled 'Synaptic Plasticity & Interneurons'.
authors.affiliation: Laboratory of Reproductive Medicine, Department of Physiology, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhou
authors.forename: Yinyang
authors.initials: Y
authors.lastname: Bai
authors.forename: Rong
authors.initials: R
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
authors.forename: Xia
authors.initials: X
authors.lastname: Chi
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sokabe
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
mesh_terms: D000395:Air Pollutants, Occupational / Q000009:adverse effects* / Q000494:pharmacology; D000679:Amygdala / Q000187:drug effects* / Q000502:physiology*; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000139:chemically induced* / Q000473:pathology; D001552:Benzazepines / Q000494:pharmacology; D001559:Benzhydryl Compounds; D001640:Bicuculline / Q000494:pharmacology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D005260:Female; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000032:analysis; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000502:physiology*; D010636:Phenols / Q000009:adverse effects* / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D000098826:Bisphenol A Compounds
chemical_list: D000395:Air Pollutants, Occupational; D001552:Benzazepines; D001559:Benzhydryl Compounds; D001640:Bicuculline; D016291:Dizocilpine Maleate; D018492:Dopamine Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D005968:Glutamate Decarboxylase; D009118:Muscimol; D010636:Phenols; D016194:Receptors, N-Methyl-D-Aspartate; C534628:SCH 23390; C402565:glutamate decarboxylase 1; C006780:bisphenol A; D000098826:Bisphenol A Compounds