Effects of environmental enrichment on behavioral deficits and alterations in hippocampal BDNF induced by prenatal exposure to morphine in juvenile rats

Ahmadalipour, Ali; Sadeghzadeh, Jafar; Vafaei, Abbas Ali; Bandegi, Ahmad Reza; Mohammadkhani, Raziyeh; Rashidy-Pour, Ali

doi:10.1016/j.neuroscience.2015.08.015

Cited by 62 publications

(39 citation statements)

References 100 publications

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“…The offspring of the heroin exposed fathers displayed differences in several measures of behavioral tasks that look into anxiety level during the EPM and OF tests. Higher entries in the closed arms that were observed in the present study were also reported by Ahmadalipour et al [36] using morphine induced female rats. We have further evaluated the anxiety level of the second generation of male heroin addicted rats.…”

Section: Discussionsupporting

confidence: 92%

Transgenerational effects of paternal heroin addiction on anxiety and aggression behavior in male offspring

et al. 2016

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BackgroundHeroin addiction is a growing concern, affecting the socioeconomic development of many countries. Little is known about transgenerational effects on phenotype changes due to heroin addiction. This study aims to investigate changes in level of anxiety and aggression up to four different generations of adult male rats due to paternal exposure to heroin.MethodsMale Sprague–Dawley rats were exposed with heroin intraperitoneally (i.p.) twice-daily for 14 days with increasing dosage regimen (F0-heroin). Male Sprague–Dawley rats (6-weeks-old) were divided into: (1) heroin exposed group (F0-heroin) and (2) control group treated with saline solution (F0-control). The dosage regime started with the lowest dose of 3 mg/kg per day of heroin followed by 1.5 mg/kg increments per day to a final dose of 13.5 mg/kg per day. Offspring were weaned on postnatal day 21. The adult male offspring from each generation were then mated with female-naïve rats after 2 weeks of heroin absence. Open field test and elevated plus maze test were used to study the anxiety level, whereas resident intruder test was used to evaluate aggression level in the addicted male rats and their offspring.ResultsHeroin exposure in male rats had resulted in smaller sizes of the litters compared to the control. We observed a higher anxiety level in the F1 and F2 progenies sired by the heroin exposed rats (F0) as compared to the control rats. Paternal heroin exposure also caused significantly more aggressive offspring in F1 compared to the control. The same pattern was also observed in the F2.ConclusionOur results demonstrated that the progenies of F1 and F2 sustained higher levels of anxiety and aggression which are due to paternal heroin exposure.

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Section: Discussionsupporting

confidence: 92%

Transgenerational effects of paternal heroin addiction on anxiety and aggression behavior in male offspring

et al. 2016

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“…In addition, findings showed that morphine exposure during the prenatal or neonate periods could trigger different long‐term effects. it was found that prenatal morphine exposure (s.c., twice daily on gestation days 11–18) reduced hippocampal BDNF levels (Ahmadalipour et al, 2015). In our previous study, we observed that morphine treatment (s.c., 5 μg, P8–P14) increased hippocampal BDNF levels on the intermediate and long term, besides, it decreased superoxide dismutase/glutathione peroxidase ratio on the long term (Rozisky et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Morphine exposure during early life alters thermal and mechanical thresholds in rats

Nunes

Medeiros

Freitas

et al. 2016

Intl J of Devlp Neuroscience

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“…However, previous models have primarily focused on the effects of prenatal morphine exposure, and only during part of the gestational period that is developmentally similar to humans in the second trimester, specifically during the rats gestation days 11 to 18. 14,[16][17][18] Only a small number of studies model opioid exposure in humans throughout pregnancy by exposing pregnant dams during both gestation and weaning. [19][20][21][22] Others have used continuous exposure to opioids, by way of implantable osmotic minipumps, 23 a model that does not mimic intermittent use in humans.…”

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confidence: 99%

Enduring consequences of perinatal fentanyl exposure in mice

Alipio

Brockett

Fox

et al. 2019

Preprint

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Opioid use by pregnant women is an understudied consequence associated with the opioid epidemic, resulting in a rise in the incidence of neonatal opioid withdrawal syndrome (NOWS), and lifelong neurobehavioral deficits that result from perinatal opioid exposure. There are few preclinical models that accurately recapitulate human perinatal drug exposure, and few focus on fentanyl, a potent synthetic opioid that is a leading driver of the opioid epidemic. To investigate the consequences of perinatal opioid exposure, we administered fentanyl to mouse dams in their drinking water throughout gestation and until litters were weaned at postnatal day (PD) 21. Fentanyl-exposed dams delivered smaller litters, and had higher litter mortality rates compared to controls.Metrics of maternal care behavior were not affected by the treatment, nor were there differences in dams' weight or liquid consumption throughout gestation and 21 days postpartum. Twenty-four hours after weaning and drug cessation, perinatal fentanyl-exposed mice exhibited signs of spontaneous somatic withdrawal behavior, and sex-specific weight fluctuations that normalized in adulthood. At adolescence (PD 35) they displayed elevated anxiety-like behaviors and decreased grooming, assayed in the elevated plus maze and sucrose splash tests. Finally, by adulthood (PD 55) they displayed impaired performance in a two-tone auditory discrimination task. Collectively, our findings suggest that perinatal fentanyl exposed mice exhibit somatic withdrawal behavior and changes across the lifespan reminiscent of humans born with NOWS.Within this growing crisis, individuals between the age of 18 and 25 have exhibited the largest increase in illicit opioid use (Substance Abuse and Mental Health Services Administration, 2013). It is concerning that women of reproductive age show increased incidence of use, given that opioids -both natural and synthetic -can readily cross the placenta and the blood-brain barrier. Indeed, in utero opioid exposure is associated with deleterious effects in developing offspring, with more dramatic effects on neurological function observed in infants relative to adults. 3 There has been an exponential increase in the distribution of the synthetic opioid, fentanyl, which is routinely incorporated into frequently used narcotics, such as heroin. 4 Fentanyl is 50 to 100 times more potent than morphine and is chiefly responsible for the recent increase in synthetic opioid-related overdose deaths. 5 The effects that synthetic opioids have on the developmental trajectory of offspring have been incompletely studied, and are critically needed to develop effective treatment and prevention plans.Women who used opioids during pregnancy have an increased rate of undergoing premature birth, stillbirth, and infant death. 6 Withdrawal symptoms occur in 30-80% of neonates exposed to opioids in utero, 7 and they exhibit decreased birth weight and body size. 8 Consequences may be long lasting, as children and adolescents exposed to pre and peri-natal opioids have disr...

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Effects of environmental enrichment on behavioral deficits and alterations in hippocampal BDNF induced by prenatal exposure to morphine in juvenile rats

Cited by 62 publications

References 100 publications

Transgenerational effects of paternal heroin addiction on anxiety and aggression behavior in male offspring

Transgenerational effects of paternal heroin addiction on anxiety and aggression behavior in male offspring

Morphine exposure during early life alters thermal and mechanical thresholds in rats

Enduring consequences of perinatal fentanyl exposure in mice

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