Neonatal domoic acid abolishes latent inhibition in male but not female rats and has differential interactions with social isolation

Marriott, Amber L.; Tasker, R. Andrew; Ryan, Catherine L.; Doucette, Tracy A.

doi:10.1016/j.neulet.2014.06.025

Cited by 12 publications

(6 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Shionogi mutant male developing rats treated with both a glutathione synthesis inhibitor or a dopamine uptake inhibitor have resulted in impaired recognition memory in NOR test in adulthood, whereas females have not been affected . Neonatal domoic acid treatment with social IS also impairs attentional processing on latent inhibition in young adult male but not in female rats . Our present results also indicated that a very simple and fast behavioral test was also appropriate to detect the presence of sex‐dependent motivational deficit instead of using really complex and time‐consuming tests predicting specific cognitive disturbances .…”

Section: Discussionsupporting

confidence: 47%

Impaired GAD1 expression in schizophrenia‐related WISKET rat model with sex‐dependent aggressive behavior and motivational deficit

Büki

Horváth

Benedek

et al. 2018

Genes Brain and Behavior

View full text Add to dashboard Cite

After peri-adolescence isolation rearing (IS) and subchronic ketamine (KET) treatment, adult, selectively bred Wistar rats (named WISKET) mimic abnormal behaviors reminiscent of human schizophrenia, including reduced prepulse-inhibition of startle reflex, disturbances in cognition, locomotor activity and thermoregulation, decreased pain sensitivity and electrophysiological alterations. To further validate our WISKET rat line, regarding its translational utility in schizophrenia research, we examined their social behavior and introduced a short and simple holeboard (HB)-like test to investigate their motivational deficit that predicts the cognitive disturbance. Sex-dependent alterations in schizophrenia may yield important insights into its etiology; thus, male and female WISKET rats were also investigated and compared with their naive Wistar counterparts. Considering the contribution of the hippocampal and cortical GABAergic inhibitory circuitry in these behavioral alterations, molecular-biology studies were also performed regarding the GAD1 gene products. Impaired social activity with increased aggression, stress-related behavior, active social withdrawal, motivation deficit and decreased exploration were observed, especially in male WISKET rats, compared with Wistar ones and their corresponding females. These alterations were accompanied by sex-dependent alterations regarding GAD67 mRNA and protein expression in the prefrontal cortex and hippocampus. In conclusion, the WISKET animals are valuable tools for animal-based preclinical drug discovery studies for predictive screening of novel compounds improving negative symptoms with potential antipsychotic efficacy.

show abstract

Section: Discussionsupporting

confidence: 47%

Impaired GAD1 expression in schizophrenia‐related WISKET rat model with sex‐dependent aggressive behavior and motivational deficit

Büki

Horváth

Benedek

et al. 2018

Genes Brain and Behavior

View full text Add to dashboard Cite

show abstract

“…This sex-dependent effect of DA also extends beyond social behaviors and includes effects on attentional processing as assessed by latent inhibition. In this task, males treated neonatally with DA showed decreased attentional processing while females were unaffected by DA treatment (85). Like with the sex ratio in susceptibility to ASD and to exposures to various toxic chemicals, males are more susceptible to in utero DA exposure than females.…”

Section: Discussionmentioning

confidence: 99%

Fetal domoic acid exposure affects lateral amygdala neurons, diminishes social investigation and alters sensory-motor gating

et al. 2016

View full text Add to dashboard Cite

Domoic acid (DA) is an algal neurotoxin that accumulates in marine fish and shellfish. DA can move across the placenta and concentrate in amniotic fluid, which can be swallowed during late gestation. DA also transfers to infants via milk. Preclinical studies to determine effects of developmental DA expose have primarily involved DA exposure during the postnatal period and little is known about late CNS effects following prenatal DA. In the present study, we tested the hypothesis that prenatal exposure of FVB mice to low levels of DA would result in diminished social interaction and sensory motor gating associated with alterations in parvalbumin immunoreactivity in relevant brain regions undergoing development during and following DA exposure. In addition to parvalbumin, we stained with NeuN for a neuronal specific nuclear protein to determine if neuronal loss followed prenatal DA exposure. A single moderate dose of DA administered during gestation produces diminishes social investigation and alters sensorimotor gating, behavioral effects more pronounced in males than females. These behavioral changes were associated with discrete alterations in the parvalbumin-positive subtype of GABAergic neurons in the dentate gyrus and lateral amygdala.

show abstract

“…Administration of low doses of DOM in neonatal rats does not produce overt toxicity or status epilepticus but results in permanent alterations in adult rat behavior that manifest as changes in cognition [17][18][19], attentional processing [20][21][22], anxiety [18,23], seizure threshold [24], and sleep patterns [25] that are consistent with the development of temporal lobe epilepsy (TLE). Moreover, these changes in behavior have been shown to correlate with neuropathological changes in the hippocampal formation such as mossy fiber sprouting (MFS) [17,26] and selective loss of parvalbumin-positive GABAergic interneurons [27] that are also present in both animal models of TLE produced by kainic acid [13,28] as well as human TLE patients [29].…”

Section: Introductionmentioning

confidence: 99%

Progressive changes in hippocampal cytoarchitecture in a neurodevelopmental rat model of epilepsy: implications for understanding presymptomatic epileptogenesis, predictive diagnosis, and targeted treatments

et al. 2017

View full text Add to dashboard Cite

Epilepsies affect about 4% of the population and are frequently characterized by a prolonged Bsilent^period before the onset of spontaneous seizures. Most current animal models of epilepsy either involve acute seizure induction or kindling protocols that induce repetitive seizures. We have developed a rat model of epilepsy that is characterized by a slowly progressing series of behavioral abnormalities prior to the onset of behavioral seizures. In the current study, we further describe an accompanying progression of cytoarchitectural changes in the hippocampal formation. Groups of male and female SD rats received serial injections of a low dose of domoic acid (0.020 mg/kg) (or vehicle) throughout the second week of life. Postmortem hippocampal tissue was obtained on postnatal days 29, 64, and 90 and processed for glial fibrillary acidic protein (GFAP), NeuN, and calbindin expression. The data revealed no significant changes on postnatal day (PND) 29 but a significant increase in hilar NeuN-positive cells in some regions on PND 64 and 90 that were identified as ectopic granule cells. Further, an increase in GFAP positive cell counts and evidence of reactive astrogliosis was found on PND 90 but not at earlier time points. We conclude that changes in cellular expression, possibly due to on-going non-convulsive seizures, develop slowly in this model and may contribute to progressive brain dysfunction that culminates in a seizure-prone phenotype.

show abstract

Neonatal domoic acid abolishes latent inhibition in male but not female rats and has differential interactions with social isolation

Cited by 12 publications

References 26 publications

Impaired GAD1 expression in schizophrenia‐related WISKET rat model with sex‐dependent aggressive behavior and motivational deficit

Impaired GAD1 expression in schizophrenia‐related WISKET rat model with sex‐dependent aggressive behavior and motivational deficit

Fetal domoic acid exposure affects lateral amygdala neurons, diminishes social investigation and alters sensory-motor gating

Progressive changes in hippocampal cytoarchitecture in a neurodevelopmental rat model of epilepsy: implications for understanding presymptomatic epileptogenesis, predictive diagnosis, and targeted treatments

Contact Info

Product

Resources

About