Prenatal ethanol exposure attenuates GABAergic inhibition in basolateral amygdala leading to neuronal hyperexcitability and anxiety-like behavior of adult rat offspring

Zhou, Rong; Wang, S.; Zhu, Xuecheng

doi:10.1016/j.neuroscience.2010.07.055

Cited by 57 publications

(52 citation statements)

References 48 publications

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“…Similarly, the human victims of the sarin terrorist attack in Japan report enduring symptoms of anxiety disorders, long after the exposure (Ohtani et al, 2004;Hoffman et al, 2007). The amygdala plays a central role in emotional behavior, and dysfunction with increased excitability of the BLA is associated with anxiety (Gonzalez et al, 1996;Shekhar et al, 2003;Zhou et al, 2010;Pidoplichko et al, 2014). The hippocampus is also significantly involved in the modulation of anxiety (Engin and Treit, 2007;Fournier and Duman, 2013).…”

Section: Efficacy Of Diazepam and Ubp302 Against Somanmentioning

confidence: 99%

The Limitations of Diazepam as a Treatment for Nerve Agent–Induced Seizures and Neuropathology in Rats: Comparison with UBP302

Apland

Aroniadou‐Anderjaska

Figueiredo

et al. 2014

J Pharmacol Exp Ther

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Exposure to nerve agents induces prolonged status epilepticus (SE), causing brain damage or death. Diazepam (DZP) is the current US Food and Drug Administration-approved drug for the cessation of nerve agent-induced SE. Here, we compared the efficacy of DZP with that of UBP302 [(S)-3-(2-carboxybenzyl) willardiine; an antagonist of the kainate receptors that contain the GluK1 subunit] against seizures, neuropathology, and behavioral deficits induced by soman in rats. DZP, administered 1 hour or 2 hours postexposure, terminated the SE, but seizures returned; thus, the total duration of SE within 24 hours after soman exposure was similar to (DZP at 1 hour) or longer than (DZP at 2 hours) that in the soman-exposed rats that did not receive the anticonvulsant. Compared with DZP, UBP302 stopped SE with a slower time course, but dramatically reduced the total duration of SE within 24 hours. Neuropathology and behavior were assessed in the groups that received anticonvulsant treatment 1 hour after exposure. UBP302, but not DZP, reduced neuronal degeneration in a number of brain regions, as well as neuronal loss in the basolateral amygdala and the CA1 hippocampal area, and prevented interneuronal loss in the basolateral amygdala. Anxiety-like behavior was assessed in the open field and by the acoustic startle response 30 days after soman exposure. The results showed that anxiety-like behavior was increased in the DZP-treated group and in the group that did not receive anticonvulsant treatment, but not in the UBP302-treated group. The results argue against the use of DZP for the treatment of nerve agent-induced seizures and brain damage and suggest that targeting GluK1-containing receptors is a more effective approach.

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Section: Efficacy Of Diazepam and Ubp302 Against Somanmentioning

confidence: 99%

The Limitations of Diazepam as a Treatment for Nerve Agent–Induced Seizures and Neuropathology in Rats: Comparison with UBP302

Apland

Aroniadou‐Anderjaska

Figueiredo

et al. 2014

J Pharmacol Exp Ther

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“…However, a striking increase in the lateral, basolateral and basomedial nuclei of the amygdala was verified (when compared to both N-SA and SC). As discussed above, these three nuclei formed the basolateral complex of the amygdala, which receives the influence of many neurotransmitter systems, such as noradrenergic, cholinergic, glutamatergic and gabaergic [48][49][50][51] and is clearly related to the emotional modulation of (Paxinos & Watson, 2007). Abbreviations: DP, dorsal peduncular cortex; IL, infralimbic cortex; PrL, prelimbic cortex; Cg1, cingulate cortex, area 1; M1, primary motor cortex; M2, secondary motor cortex; Fr3, frontal cortex, area 3; S1J, primary somatosensory cortex, jaw region; GI, granular insular cortex; DI, dysgranular insular cortex; AID, agranular insular cortex; LO, lateral orbital cortex; AcbC, accumbens nucleus, core; AcbSh, accumbens nucleus, shell; DEn, dorsal endopiriform nucleus; Pir, piriform cortex.…”

Section: Relationship Between Increases In 7 Density and Memory Maintmentioning

confidence: 99%

Chronic Infusion of Amyloid-β Peptide and Sustained Attention Altered α7 Nicotinic Receptor Density in the Rat Brain

Viel

Caetano²,

Albuquerque³

et al. 2012

CAR

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2012Chronic infusion of amyloid-peptide and sustained attention altered 7 nicotinic receptor density in the rat brain Current Alzheimer Research, Sharjah, v. 9, n. 10, supl., Part 2, pp. 1210-1220, dec, 2012 Abstract: It is already known that progressive degeneration of cholinergic neurons in brain areas such as the hippocampus and the cortex leads to memory deficits, as observed in Alzheimer's disease. This work verified the effects of the infusion of amyloid-(A ) peptide associated to an attentional rehearsal on the density of 7 nicotinic cholinergic receptor (nAChR) in the brain of male Wistar rats. Animals received intracerebroventricular infusion of A or vehicle (control -C) and their attention was stimulated weekly (Stimulated A group: S-A and Stimulated Control group: SC) or not (NonStimulated A group: N-SA and Non-Stimulated Control group: N-SC), using an active avoidance apparatus. Conditioned avoidance responses (CAR) were registered. Chronic infusion of A caused a 37% reduction in CAR for N-SA . In S-A , this reduction was not observed. At the end, brains were extracted and autoradiography for 7 nAChR was conducted using [125 I]--bungarotoxin. There was an increase in 7 density in hippocampus, cortex and amygdala of SA animals, together with the memory preservation. In recent findings from our lab using mice infused with A and the 7 antagonist methyllycaconitine, and stimulated weekly in the same apparatus, it was observed that memory maintenance was abolished. So, the increase in 7 density in brain areas related to memory might be related to a participation of this receptor in the long-lasting change in synaptic plasticity, which is important to improve and maintain memory consolidation.

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“…To our knowledge, this is the first demonstration of heightened anxiety in FAE rats during early adolescence. Previous studies have demonstrated increased anxiety and depressive behaviors in adult FAE rats [60, [80][81][82], however see [83]. Children diagnosed with FASD exhibit high anxiety [84,85], as well as a remarkably high prevalence of epilepsy [86].…”

mentioning

confidence: 98%

“…Children diagnosed with FASD exhibit high anxiety [84,85], as well as a remarkably high prevalence of epilepsy [86]. While other mechanisms may also be involved, decrements in GABAergic neurotransmission have been associated with increased anxiety [29,30,81] and reduced seizure thresholds [33,87].…”

mentioning

confidence: 99%

Dihydromyricetin Prevents Fetal Alcohol Exposure-Induced Behavioral and Physiological Deficits: The Roles of GABAA Receptors in Adolescence

et al. 2014

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Fetal alcohol exposure (FAE) can lead to a variety of behavioral and physiological disturbances later in life. Understanding how alcohol (ethanol, EtOH) affects fetal brain development is essential to guide the development of better therapeutics for FAE. One of EtOH's many pharmacological targets is the c-aminobutyric acid type A receptor (GABA A R), which plays a prominent role in early brain development. Acute EtOH potentiates inhibitory currents carried by certain GABA A R subtypes, whereas chronic EtOH leads to persistent alterations in GABA A R subunit composition, localization and function. We recently introduced a flavonoid compound, dihydromyricetin (DHM), which selectively antagonizes EtOH's intoxicating effects in vivo and in vitro at enhancing GABA A R function as a candidate for alcohol abuse pharmacotherapy. Here, we studied the effect of FAE on physiology, behavior and GABA A R function of early adolescent rats and tested the utility of DHM as a preventative treatment for FAE-induced disturbances. Gavage administration of EtOH (1.5, 2.5, or 5.0 g/kg) to rat dams on day 5, 8, 10, 12, and 15 of pregnancy dose-dependently reduced female/male offspring ratios (largely through decreased numbers of female offspring) and offspring body weights. FAE (2.5 g/kg) rats tested on postnatal days (P) 25-32 also exhibited increased anxiety and reduced pentylenetetrazol (PTZ)-induced seizure threshold. Patchclamp recordings from dentate gyrus granule cells (DGCs) in hippocampal slices from FAE (2.5 g/kg) rats at P25-35 revealed reduced sensitivity of GABAergic miniature inhibitory postsynaptic currents (mIPSCs) and tonic current (I tonic ) to potentiation by zolpidem (0.3 lM). Interestingly, potentiation of mIPSCs by gaboxadol increased, while potentiation of I tonic decreased in DGCs from FAE rats. Coadministration of EtOH (1.5 or 2.5 g/kg) with DHM (1.0 mg/kg) in pregnant dams prevented all of the behavioral, physiological, and pharmacological alterations observed in FAE offspring. DHM administration alone in pregnant rats had no adverse effect on litter size, progeny weight, anxiety level, PTZ seizure threshold, or DGC GABA A R function. Our results indicate that FAE induces long-lasting alterations in physiology, behavior, and hippocampal GABA A R function and that these deficits are prevented by DHM co-treatment of EtOH-exposed dams. The absence of adverse side effects and the ability of DHM to prevent FAE consequences suggest that DHM is an attractive candidate for development as a treatment for prevention of fetal alcohol spectrum disorders.

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Prenatal ethanol exposure attenuates GABAergic inhibition in basolateral amygdala leading to neuronal hyperexcitability and anxiety-like behavior of adult rat offspring

Cited by 57 publications

References 48 publications

The Limitations of Diazepam as a Treatment for Nerve Agent–Induced Seizures and Neuropathology in Rats: Comparison with UBP302

The Limitations of Diazepam as a Treatment for Nerve Agent–Induced Seizures and Neuropathology in Rats: Comparison with UBP302

Chronic Infusion of Amyloid-β Peptide and Sustained Attention Altered α7 Nicotinic Receptor Density in the Rat Brain

Dihydromyricetin Prevents Fetal Alcohol Exposure-Induced Behavioral and Physiological Deficits: The Roles of GABAA Receptors in Adolescence

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Prenatal ethanol exposure attenuates GABAergic inhibition in basolateral amygdala leading to neuronal hyperexcitability and anxiety-like behavior of adult rat offspring

Cited by 57 publications

References 48 publications

The Limitations of Diazepam as a Treatment for Nerve Agent–Induced Seizures and Neuropathology in Rats: Comparison with UBP302

The Limitations of Diazepam as a Treatment for Nerve Agent–Induced Seizures and Neuropathology in Rats: Comparison with UBP302

Chronic Infusion of Amyloid-&beta; Peptide and Sustained Attention Altered &alpha;7 Nicotinic Receptor Density in the Rat Brain

Dihydromyricetin Prevents Fetal Alcohol Exposure-Induced Behavioral and Physiological Deficits: The Roles of GABAA Receptors in Adolescence

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Chronic Infusion of Amyloid-β Peptide and Sustained Attention Altered α7 Nicotinic Receptor Density in the Rat Brain