Proconvulsant effect of post-weaning social isolation stress may be associated with dysregulation of opioid system in the male mice

• Published in: Medical hypotheses 2015-05, Vol.84 (5), p.445-447
• Main Authors: Imran Khan, Muhammad, Shirzadian, Armin, Haj-Mirzaian, Arya, Mehr, Shahram Ejtemaei, Dehpour, Ahmad Reza, Rahimi-Balaei, Maryam, Amiri, Shayan
• Format: Article
• Language: English
• Subjects: Animals; Brain - metabolism; Convulsants - pharmacology; Internal Medicine; Male; Mice; Models, Biological; Morphine - pharmacology; Pentylenetetrazole; Receptors, Opioid, mu - metabolism; Seizures - etiology; Social Isolation - psychology; Stress, Psychological - physiopathology
• ISSN: 0306-9877; 1532-2777
• DOI: 10.1016/j.mehy.2015.01.041

Abstract Opioid system has been reported to be involved in the consequences of post-weaning social isolation stress (SIS) such as hypoalgesia and social behaviors. Also, previous studies have shown that SIS increases mu opioid receptor expression in the regions of the brain associated with epileptogenesis such as basolateral amygdala and cortex. Interestingly, experiencing SIS increases seizure risk in the adulthood. Regarding the SIS-induced alterations in the opioid system, we hypothesize that increase in opioidergic system activity (mostly by mu receptor) may be associated with increase in vulnerability to seizures. In non-stressed mice, morphine at low doses (1 mg/kg) has an anticonvulsant effect on seizure threshold while higher doses (60 mg/kg) are proconvulsant. To support the hypothesis, we showed that administration of anticonvulsant dose of morphine (1 mg/kg) to socially isolated male mice not only was not able to reverse the negative effect of SIS on seizure susceptibility to pentylenetetrazole but also enhanced it. These results support our hypothesis that proconvulsant effect of post-weaning social isolation stress may be associated with dysregulation of opioid system in the adult male mice.