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

• Published in: International journal of developmental neuroscience Vol. 60; no. 1; pp. 56 - 62
• Main Authors: Panahi, Yousef, Saboory, Ehsan, Rassouli, Ali, Sadeghi-Hashjin, Goudarz, Roshan-Milani, Shiva, Derafshpour, Leila, Rasmi, Yousef
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01-08-2017; Elsevier BV
• Subjects: Action Potentials - drug effects; Acute; Animals; Animals, Newborn; Antagonist drugs; Attention; Brain; Brain slice preparation; Cells, Cultured; Cerebrospinal fluid; Chronic; Convulsions & seizures; Developing brain; Dose-Response Relationship, Drug; Drug dependence; Enkephalins; Epilepsy; Epilepsy - drug therapy; Epilepsy - etiology; Epilepsy - physiopathology; Female; Hippocampal slices; Hippocampus; Hippocampus - drug effects; Hippocampus - physiopathology; Male; Mice; Morphine; Morphine Dependence - complications; Morphine Dependence - drug therapy; Morphine Dependence - physiopathology; Narcotic Antagonists - administration & dosage; Narcotics; Opioid receptors; Opioid receptors (type mu); Receptors; Receptors, Opioid - agonists; Rodents; Seizure; Treatment Outcome; Developing brain; Hippocampal slices; Morphine; Chronic; Seizure; Acute
• ISSN: 0736-5748; 1873-474X
• DOI: 10.1016/j.ijdevneu.2017.04.003

•Excitatory effect of opiate on epileptiform activity is mediated through K receptor.•Inhibitory effect of opiate on epileptiform activity is mediated via the μ receptor.•The pattern of effect is similar in normal and morphine-dependent slices.•But the intensity of the effect is significantly stronger in normal mice.•Exposure to morphine in neonatal period alters brain susceptibility to seizure later in life.
Hippocampal slices of mouse brain were used to estimate how selective agonist and antagonist of opioid receptors alter Low-Mg+2 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.