Experiencing neonatal maternal separation increased the seizure threshold in adult male mice: Involvement of the opioid system

Amini-Khoei, Hossein; Amiri, Shayan; Shirzadian, Armin; Haj‐Mirzaian, Arya; Alijanpour, Sakineh; Rahimi-Balaei, Maryam; Mohammadi-Asl, Ali; Hassanipour, Mahsa; Mehr, Shahram Ejtemaie; Dehpour, Ahmad Reza

doi:10.1016/j.yebeh.2015.08.025

Cited by 28 publications

(16 citation statements)

References 36 publications

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“…NTX inhibits all three kinds of opioid receptors (µ, κ, and δ). We used a noneffective dose of NTX that did not have a significant impact on seizure threshold . Moreover, methadone has high affinity for µ‐opioid receptors .…”

Section: Discussionmentioning

confidence: 99%

Methadone's effects on pentylenetetrazole‐induced seizure threshold in mice: NMDA/opioid receptors and nitric oxide signaling

Roodsari

Bahramnejad

Rahimi

et al. 2019

Annals of the New York Academy of Sciences

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Methadone is a synthetic opioid used to treat opiate withdrawal and addiction. Studies have demonstrated the impact of methadone on seizure susceptibility. This study investigated the modulatory impacts of acute and subchronic (three times daily for 5 days) intraperitoneal methadone treatment on pentylenetetrazole‐induced clonic seizure threshold (CST) in mice, as well as the involvement of the nitric oxide, N‐methyl‐d‐aspartate (NMDA), and µ‐opioid pathways. Acute administration of different doses of methadone (0.1, 0.3, 1, and 3 mg/kg) 45 min before CST significantly decreased the seizure threshold. Additionally, pretreatment with noneffective doses of an opioid receptor antagonist (naltrexone) and NMDA receptor antagonists (ketamine and MK‐801) inhibited methadone's proconvulsive activity in the acute phase, while l‐NAME (a nonspecific nitric oxide synthase (NOS) inhibitor) did not affect that activity. In the subchronic phase, methadone (3 mg/kg) demonstrated an anticonvulsive effect. Although subchronic pretreatment with noneffective doses of l‐NAME and 7‐nitroindazole (a specific neuronal NOS inhibitor) reversed methadone's anticonvulsive activity, aminoguanidine (a specific inducible NOS inhibitor), naltrexone, MK‐801, and ketamine did not change methadone's anticonvulsive characteristic. Our results suggest that NMDA and µ‐opioid receptors may be involved in methadone's proconvulsive activity in the acute phase, while methadone's anticonvulsive activity may be modulated by neuronal NOS in the subchronic phase.

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Section: Discussionmentioning

confidence: 99%

Methadone's effects on pentylenetetrazole‐induced seizure threshold in mice: NMDA/opioid receptors and nitric oxide signaling

Roodsari

Bahramnejad

Rahimi

et al. 2019

Annals of the New York Academy of Sciences

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“…Therefore, given that the nociceptive system of rats matures during the first three postnatal weeks (Bernardi et al, 1986; Kwok et al, 2014; Amini‐Khoei et al, 2015), postnatal maternal deprivation is considered to bean early life stressor and was indicated to have lasting effects, such as the nociceptive response. In fact, animals and humans subjected to stressors were found to exhibit higher pain thresholds (Butler and Finn, 2009; al'Absi et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, long-lasting functional and structural modifications induced by postnatal stress (Kaufman et al, 2000) occur in several levels of developmental (i.e., growth (Kuhn and Schanberg, 1998)), and regulatory systems maturation (Ladd et al, 2000), as well as in the learning process (McEwen, 2001). Therefore, given that the nociceptive system of rats matures during the first three postnatal weeks (Bernardi et al, 1986;Kwok et al, 2014;Amini-Khoei et al, 2015), postnatal maternal deprivation is considered to bean early life stressor and was indicated to have lasting effects, such as the nociceptive response. In fact, animals and humans subjected to stressors were found to exhibit higher pain thresholds (Butler and Finn, 2009;al'Absi et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Maternal deprivation alters nociceptive response in a gender‐dependent manner in rats

Ströher

Oliveira

Lopes

et al. 2019

Intl J of Devlp Neuroscience

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The present study aimed at investigating both the early and long‐term effects of maternal deprivation as well as gender on neuromotor reflexes, anxiety behavior and thermal nociceptive responses. A total of 64 Wistar rats pups (32 males, 32 females) were utilized and were deprived of their mother for 3 h/daily, from postnatal day 1 (P1) until P10. Successively, animals were divided into 2 groups: control group (C) ‐ pups no subjected to intervention; and the maternal‐deprived group (MD): pups subjected to maternal deprivation. The neuromotor reflexes were evaluated through the righting reflex and negative geotaxis tests; the exploratory behavior by open field test (OFT); the anxiety‐like behavior by elevated plus‐maze test (EPM); the thermal nociceptive responses byhot plate (HP) and tail‐flick (TFL) tests. All the animals subjected to maternal deprivation showed a delayed reflex response at P8 in the negative geotaxis test. In contrast, the OFT at P20 identified an effect of gender on the outer crossings and grooming as well as an interaction between gender and maternal deprivation on latency. Additionally, effect of maternal deprivation in the open and closed arms as well as gender effect in the protected head‐dipping (PHD) and non‐protected head‐dipping (NPHD) were observed at P20 (EPM). In contrast, there were a gender effect on latency and an interaction between gender and maternal deprivation on rearing at P42. Moreover, in nociceptive tests was observed an analgesic effect induced by maternal deprivation; however, in the TFL test, only deprived females showed this effect. Surprisingly, only control animals presented an ontogeny nociceptive effect in the HP testat P21 and P43, which may be related to an increase in the inhibitory nociceptive pathways throughout life. In this way, we suggest maternal deprivation to be able to anticipate the maturation of the inhibitory nociceptive pathway. In conclusion, maternal deprivation induced a delayed reflex response at P8 and altered the anxiety and nociceptive behaviors according to the time after exposure to this stressor, in a gender‐specific manner.

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“…We considered the birth date to be postnatal day 0 (PND 0). The offspring at PND 2 were subjected to MS model [25,26]. In this paradigm, pups were detached from their mothers for 3 h daily from PND 2-14 (at 09: 00-12: 00 am) and then were returned to their mothers.…”

Section: Animals and Housing Conditionsmentioning

confidence: 99%

Trigonelline through the Attenuation of Oxidative Stress Exerts Antidepressant- and Anxiolytic-Like Effects in a Mouse Model of Maternal Separation Stress

et al. 2019

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Depression and anxiety are common psychiatric disorders accounting for social and economic burdens. Previous studies have shown that oxidative stress and oxidant/antioxidant imbalance are involved in the pathophysiology of psychiatric disorders. Experiencing early-life adversities (like maternal separation [MS] stress) provoked psychiatric disorders. Trigonelline (TRG) is a pyridine alkaloid that has various pharmacological effects including hypoglycemic, neuroprotective and memory-improving properties. To investigate the antidepressant-and anxiolytic-like effects of TRG focusing oxidative stress, we applied the MS paradigm to male mice at postnatal day (PND) 2-14 (3 h daily, 9-12 a.m.) and investigated the behaviors at PND 45-47. Using valid behavioral tests including a forced swimming test (FST), splash test, open field test (OFT) and elevated plus maze (EPM), we investigated behavioral modifications. Additionally, we examined the effects of MS and TRG treatment on the level of malondialdehyde (MDA), nitric oxide (NO) and also antioxidant capacity in the brain and serum. Our results showed that MS provoked depressive-and anxiety-like behaviors in the FST, OFT, EPM and splash test, which are associated with an increase in MDA and NO levels as well as a decrease in antioxidant capacity in the brain and serum samples. Findings determined that TRG significantly reversed the negative effects of MS on behavior that is accompanied by a decrease in MDA and NO as well as an increase in antioxidant capacity. Findings of the present study showed that beneficial effects of TRG may be, at least partially, mediated via the reduction of oxidative stress and an increase of antioxidant capacity.

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Experiencing neonatal maternal separation increased the seizure threshold in adult male mice: Involvement of the opioid system

Cited by 28 publications

References 36 publications

Methadone's effects on pentylenetetrazole‐induced seizure threshold in mice: NMDA/opioid receptors and nitric oxide signaling

Methadone's effects on pentylenetetrazole‐induced seizure threshold in mice: NMDA/opioid receptors and nitric oxide signaling

Maternal deprivation alters nociceptive response in a gender‐dependent manner in rats

Trigonelline through the Attenuation of Oxidative Stress Exerts Antidepressant- and Anxiolytic-Like Effects in a Mouse Model of Maternal Separation Stress

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