Morphine exposure induces age‐dependent alterations in pentylenetetrazole‐induced epileptic behaviors in prepubertal rats

Developmental Psychobiology

Roshan‐Milani

et al. 2014

Self Cite

Prenatal exposure to stress and morphine has complicated effects on epileptic seizure. Many reports have shown an interaction between morphine- and stress-induced behavioral changes in adult rats. In the present study, effect of prenatal forced-swim stress and morphine co-administration on pentylentetrazole (PTZ)-induced epileptic behaviors was investigated in rat offspring to address effect of the interaction between morphine and stress. Pregnant rats were divided to four groups of control-saline, control-morphine, stressed-saline and stressed-morphine. In the stressed group, the rats were placed in 25 °C water on 17-19 days of pregnancy. In the morphine/saline group, the rats received morphine/saline on the same days. In the morphine/saline-stressed group, they were exposed to stress and received morphine/saline simultaneously. On postnatal day 15 (P15), blood samples were collected to determine corticosterone (COS) level. On P15 and P25, PTZ was injected to the rest of pups to induce seizure. Then, epileptic behaviors of each rat were individually observed. Latency of tonic-colonic seizures decreased in control-morphine and stressed-saline groups while increasing in stressed-morphine rats compared to control-saline group on P15. Duration of tonic-colonic seizures significantly increased in control-morphine and stressed-saline rats compared to stressed-morphine and control-saline rats on P15, but not P25. COS levels increased in stressed-saline group but decreased in control-morphine group compared to control-saline rats. Body weight was significantly higher in morphine groups than saline treated rats. Prenatal exposure to forced-swim stress potentiated PTZ-induced seizure in the offspring rats. Co-administration of morphine attenuated effect of stress on body weight, COS levels, and epileptic behaviors.

Section: Discussionsupporting

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Effect of prenatal forced‐swim stress and morphine co‐administration on pentylentetrazol‐induced epileptic behaviors in infant and prepubertal rats

Ebrahimi

Developmental Psychobiology

Roshan‐Milani

et al. 2014

Self Cite

“…Then, male rats ( n = 43) were randomly divided into three groups: saline (S; n = 17), morphine (M; n = 14) and tramadol (T; n = 12). Pups in the morphine and tramadol groups were injected with morphine or tramadol (5 mL/kg, s.c.) on the back, above the tail, at doses of 3, 6, 9, 12, 15, 18 and 21 mg/kg on P8, P9, P10, P11, P12, P13 and P14, respectively . Similar doses of morphine and tramadol were used to simplify the comparison of the effects of these drugs on anxiety.…”

Section: Methodsmentioning

confidence: 99%

“…Pups in the morphine and tramadol groups were injected with morphine or tramadol (5 mL/kg, s.c.) on the back, above the tail, at doses of 3, 6, 9, 12, 15, 18 and 21 mg/kg on P8, P9, P10, P11, P12, P13 and P14, respectively. 41,42 Similar doses of morphine and tramadol were used to simplify the comparison of the effects of these drugs on anxiety. Pups in the saline group were injected with an equal volume of saline solution (5 mL/kg).…”

Section: Morphine and Tramadol Administrationmentioning

confidence: 99%

Chronic morphine and tramadol re‐exposure induced an anti‐anxiety effect in prepubertal rats exposed neonatally to the same drugs

Gholami

Khalkhali

2014

Clin Exp Pharma Physio

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Anxiety disorders are among the most common mental disorders. Drugs that are often administered to manage medical problems cause rebound anxiety. The use of morphine and tramadol has increased in recent decades. In the present study, the effects of morphine and tramadol exposure during the neonatal and prepubertal periods on anxiety-like behaviours in prepubertal rats were investigated. Male neonate rats were injected subcutaneously with saline, morphine or tramadol (3-21 mg/kg) on a daily basis from postnatal Day (P) 8 to P14. On P22, rats were divided into seven groups (saline/saline, saline/tramadol, saline/morphine, tramadol/saline, tramadol/tramadol, morphine/saline and morphine/morphine) and were injected with saline, tramadol or morphine for seven consecutive days. All rats were tested in an elevated plus maze (EPM) on P24 (acute effects), P27 (chronic effects) and P29. Locomotor activity was increased by the second and third exposure to the EPM. Re-exposure to chronic morphine and tramadol resulted in increased locomotor activity, whereas acute and chronic administration of these drugs induced no notable difference. Anxiety decreased markedly after re-exposure to tramadol and this anxiolytic-like behaviour was more dominant in EPM re-exposure in rats that had received higher doses of tramadol. Re-exposure to tramadol elicited a stronger anxiolytic-like behaviour than re-exposure to morphine. It can be concluded that repeated morphine and tramadol administration during the neonatal period followed by re-exposure to these drugs at an immature stage produces considerable anxiolytic-like behaviour. Exposure to chronic morphine and tramadol during the neonatal period may affect the developing brain, which may induce long-term changes in the opioid response.

“…The evaluation of the postictal seizure suppression after a fully kindled seizure demonstrates that morphine‐pretreated rats have a decreased sensitivity to subsequent kindling stimulations (Hofmann et al, 2006). It has also been reported that early exposure to chronic morphine in infant rats might change their susceptibility to PTZ‐induced seizure in an age‐dependent manner (Gholami and Saboory, 2013; Gholami et al, 2014). Previous studies have demonstrated that chronic opiate exposure during infancy affects the developing brain and alters the number and sensitivity of opioid receptors throughout life (Thornton and Smith, 1998).…”

Section: Discussionmentioning

confidence: 99%

The effect of selective opioid receptor agonists and antagonists on epileptiform activity in morphine‐dependent infant mice hippocampal slices

Panahi

Intl J of Devlp Neuroscience

Rabbani

et al. 2017

Self Cite

Hippocampal slices of mouse brain were used to estimate how selective agonist and antagonist of opioid receptors alter Low-Mg artificial cerebrospinal fluid (LM-ACSF)-induced epileptiform activities in normal and morphine-dependent mice. Brain slices were obtained from control and morphine-dependent mice. The morphine-dependent group received morphine once a day for 5 consecutive days, and the control group received saline. All injections were administered subcutaneously (s.c) in a volume of 0.1mL on postnatal days 14-18. Brain slices were perfused with LM-ACSF along with selective agonist and antagonist of μ, κ and δ opioid receptors. Changes in spike count per unit of time were used as indices to quantify the effects of LM-ACSF exposure in the slices. In both groups, DAMGO (selective μ opioid receptor agonist) and DPDPE (selective δ opioid receptor agonist) suppressed while Dyn-A (selective κ opioid receptor agonist) potentiated the epileptiform activity. Meanwhile, BFN-A (selective μ opioid receptor antagonist) recovered epileptiform activity in normal brain slices but not in morphine-dependent ones. NTI (selective δ opioid receptor antagonist) and nor-BNI (selective κ opioid receptor antagonist) decreased epileptiform activity. It seems that the excitatory effect of morphine on epileptiform activity was mediated through kappa receptors and its inhibitory effect was mediated via the mu receptor and, to a lesser degree, through the delta receptor. The pattern of effect was similar in normal and morphine-dependent slices, but the intensity of the effect was significantly stronger in normal mice. Finding of this study might be considered for further research and attention in epilepsy treatment.