Increased anxiety-like behaviour and altered GABAergic system in the amygdala and cerebellum of VPA rats — An animal model of autism

Olexová, Lucia; Štefánik, Peter; Kršková, Lucia

doi:10.1016/j.neulet.2016.06.035

Cited by 63 publications

(51 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Anxiety is often seen in ASD (Gillott et al, 2001; MacNeil et al, 2009; Olexová et al, 2016), and developmental exposure to SSRIs in rodents leads to increased anxiety‐like behavior (Ansorge et al, 2008, 2004; Bairy et al, 2007; Karpova et al, 2009; Noorlander et al, 2008; Olivier et al, 2011b; Sarkar et al, 2014; Soga et al, 2012; Zohar et al, 2016). We showed that perinatal exposure to 10 mg/kg CIT increased anxiety in open‐field and marble burying (Sprowles et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…ASD children have impaired social interactions (MacNeil et al, 2009; Olexová et al, 2016), and studies report decreased social preference and/or increased depressive‐like behavior in rodents developmentally exposed to SSRIs (Ansorge et al, 2004; Boulle et al, 2016; Glover et al, 2015; Olivier et al, 2011b; Rebello et al, 2014; Rodriguez‐Porcel et al, 2011; Sarkar et al, 2014; Zohar et al, 2016). We showed that perinatal exposure to 10 mg/kg CIT increased behavioral despair in the FST but did not affect social preference (Sprowles et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…ASD children have impaired social interactions (MacNeil et al, 2009;Olexová et al, 2016), and studies report decreased social preference and/or increased depressive-like behavior in rodents developmentally exposed to SSRIs (Ansorge et al, 2004;Boulle et al, 2016;Glover et al, 2015;Olivier et al, 2011b;Rebello et al, 2014; J.L.N. Sprowles et al International Journal of Developmental Neuroscience 61 (2017) 92-111 Rodriguez -Porcel et al, 2011;Sarkar et al, 2014;Zohar et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Differential effects of perinatal exposure to antidepressants on learning and memory, acoustic startle, anxiety, and open‐field activity in Sprague‐Dawley rats

Sprowles¹,

Hufgard

Gutierrez

et al. 2017

Intl J of Devlp Neuroscience

View full text Add to dashboard Cite

Most antidepressants inhibit monoamine reuptake. Selective serotonin (5-HT) reuptake inhibitors (SSRIs) act on the 5-HT transporter (SERT) whereas norepinephrine-dopamine reuptake inhibitors (NDRIs) act on the norepinephrine and dopamine transporters. Epidemiological reports link SSRI use during pregnancy to an increased prevalence of autism spectrum disorder (ASD). We previously showed that perinatal exposure to the SSRI citalopram (CIT) results in rodent offspring that exhibit a number of behaviors consistent with an ASD-like phenotype. The present study examined the effect of perinatal exposure to CIT (at a lower dose), another SSRI, fluoxetine (FLX), and an NDRI, bupropion (BUP). Gravid Sprague-Dawley rats were subcutaneously injected twice per day (6h apart) with 5mg/kg CIT, 5mg/kg FLX, 15mg/kg BUP, or saline (SAL) from embryonic day (E) 6-21, and directly to the pups from postnatal day (P) 1-20. As adults, one male/female from each litter was given one of a series of tests. Both SSRI-exposed groups showed spatial learning deficits in Morris and radial water mazes, increased marble burying, increased acoustic startle, hypoactivity, and attenuated activity to the stimulating effect of the NMDA-R antagonist MK-801. The BUP-exposed group showed a reduction in elevated zero-maze quadrant entries and increased stimulated open-field activity following (+)-amphetamine challenge. These results reinforce concern about the use of antidepressants during pregnancy and highlight how the two classes of drugs produce different constellations of effects with more effects associated with the SSRIs. Further investigation into how antidepressants alter brain development leading to enduring adverse neurobehavioral effects is warranted.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Differential effects of perinatal exposure to antidepressants on learning and memory, acoustic startle, anxiety, and open‐field activity in Sprague‐Dawley rats

Sprowles¹,

Hufgard

Gutierrez

et al. 2017

Intl J of Devlp Neuroscience

View full text Add to dashboard Cite

show abstract

“…ASD patients often exhibit anxiety (Gillott et al, 2001; MacNeil et al, 2009; Olexová et al, 2016), and there are numerous reports of increased anxiety‐ and depressive‐like behavior in rodents developmentally exposed to SSRIs (Ansorge et al, 2004; Glover et al, 2015; Hansen et al, 1997; Noorlander et al, 2008; Popa et al, 2008). The current results corroborate such findings.…”

Section: Discussionmentioning

confidence: 99%

Perinatal exposure to the selective serotonin reuptake inhibitor citalopram alters spatial learning and memory, anxiety, depression, and startle in Sprague‐Dawley rats

Sprowles¹,

Hufgard

Gutierrez

et al. 2016

Intl J of Devlp Neuroscience

View full text Add to dashboard Cite

Selective serotonin reuptake inhibitors (SSRIs) block the serotonin (5-HT) reuptake transporter (SERT) and increase synaptic 5-HT. 5-HT is also important in brain development; hence when SSRIs are taken during pregnancy there exists the potential for these drugs to affect CNS ontogeny. Prenatal SSRI exposure has been associated with an increased prevalence of autism spectrum disorder (ASD), and peripheral 5-HT is elevated in some ASD patients. Perinatal SSRI exposure in rodents has been associated with increased depression and anxiety-like behavior, decreased sociability, and impaired learning in the offspring, behaviors often seen in ASD. The present study investigated whether perinatal exposure to citalopram causes persistent neurobehavioral effects. Gravid Sprague-Dawley rats were assigned to two groups and subcutaneously injected twice per day with citalopram (10mg/kg; Cit) or saline (Sal) 6h apart on embryonic day (E)6-21, and then drug was given directly to the pups after delivery from postnatal day (P)1-20. Starting on P60, one male/female from each litter was tested in the Cincinnati water maze (CWM) and open-field before and after MK-801. A second pair from each litter was tested in the Morris water maze (MWM) and open-field before and after (+)-amphetamine. A third pair was tested as follows: elevated zero-maze, open-field, marble burying, prepulse inhibition of acoustic startle, social preference, and forced swim. Cit-exposed rats were impaired in the MWM during acquisition and probe, but not during reversal, shift, or cued trials. Cit-exposed rats also showed increased marble burying, decreased time in the center of the open-field, decreased latency to immobility in forced swim, and increased acoustic startle across prepulse intensities with no effects on CWM. The results are consistent with citalopram inducing several ASD-like effects. The findings add to concerns about use of SSRIs during pregnancy. Further research on different classes of antidepressants, dose-effect relationships, timing of exposure periods, and mechanisms for these effects are needed. It is also important to balance the effects described here against the effects of the disorders for which the drugs are given.

show abstract

“…It is known that glutamic acid decarboxylase (GAD67) expression in VPA-exposed female hippocampus is higher compared with male offspring (Kim et al, 2013). However, it has recently been shown that adult VPA rats had increased mRNA expression for GABA transporter 1 in the amygdala and decreased levels of GAD67 and GAD65 in the cerebellum compared to control animals, in both genders (Olexová, Štefánik & Kršková, 2016). These data suggest that the mechanisms responsible for gender specificity in ASD and epilepsy can involve different brain areas.…”

Section: Discussionmentioning

confidence: 99%

Pentylenetetrazole-induced seizures in developing rats prenatally exposed to valproic acid

Puig-Lagunes

Manzo

Beltran-Parrazal

et al. 2016

PeerJ

View full text Add to dashboard Cite

BackgroundEpidemiological evidence indicates epilepsy is more common in patients with autism spectrum disorders (ASD) (20–25%) than in the general population. The aim of this project was to analyze seizure susceptibility in developing rats prenatally exposed to valproic acid (VPA) as autism model.MethodsPregnant females were injected with VPA during the twelfth embryonic day. Seizures were induced in fourteen-days-old rat pups using two models of convulsions: pentylenetetrazole (PTZ) and lithium-pilocarpine (Li-Pilo).ResultsTwo subgroups with different PTZ-induced seizure susceptibility in rats exposed to VPA were found: a high susceptibility (VPA+) (28/42, seizure severity 5) and a low susceptibility (VPA−) (14/42, seizure severity 2). The VPA+ subgroup exhibited an increased duration of the generalized tonic-clonic seizure (GTCS; 45 ± 2.7 min), a higher number of rats showed several GTCS (14/28) and developed status epilepticus (SE) after PTZ injection (19/27) compared with control animals (36.6 ± 1.9 min; 10/39; 15/39, respectively). No differences in seizure severity, latency or duration of SE induced by Li-Pilo were detected between VPA and control animals.DiscussionPrenatal VPA modifies the susceptibility to PTZ-induced seizures in developing rats, which may be linked to an alteration in the GABAergic transmission. These findings contribute to a better understanding of the comorbidity between autism and epilepsy.

show abstract

Increased anxiety-like behaviour and altered GABAergic system in the amygdala and cerebellum of VPA rats — An animal model of autism

Cited by 63 publications

References 39 publications

Differential effects of perinatal exposure to antidepressants on learning and memory, acoustic startle, anxiety, and open‐field activity in Sprague‐Dawley rats

Differential effects of perinatal exposure to antidepressants on learning and memory, acoustic startle, anxiety, and open‐field activity in Sprague‐Dawley rats

Perinatal exposure to the selective serotonin reuptake inhibitor citalopram alters spatial learning and memory, anxiety, depression, and startle in Sprague‐Dawley rats

Pentylenetetrazole-induced seizures in developing rats prenatally exposed to valproic acid

Contact Info

Product

Resources

About