morphinans and Epilepsy

Epilepsy is a common neurological disorder and is not well controlled by available antiepileptic drugs (AEDs). Inflammation is considered to be a critical factor in the pathophysiology of epilepsy. Sinomenine (SN), a bioactive alkaloid with anti-inflammatory effect, exerts neuroprotective activity in many nervous system diseases. However, little is known about the effect of SN on epilepsy.. The chronic epilepsy model was established by pentylenetetrazole (PTZ) kindling. Morris water maze (MWM) was used to test spatial learning and memory ability. H.E. staining and Hoechst 33258 staining were used to evaluate hippocampal neuronal damage. The expression of nucleotide oligomerization domain (NOD)-like receptor protein 1 (NLRP1) inflammasome complexes and the level of inflammatory cytokines were determined by western blot, quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA) kits.. SN (20, 40, and 80 mg/kg) dose-dependently disrupts the kindling acquisition process, which decreases the seizure scores and the incidence of fully kindling. SN also increases the latency of seizure and decreases the duration of seizure in fully kindled rats. In addition, different doses of SN block the hippocampal neuronal damage and minimize the impairment of spatial learning and memory in PTZ kindled rats. Finally, PTZ kindling increases the expression of NLRP1 inflammasome complexes and the levels of inflammatory cytokines IL-1β, IL-18, IL-6, and TNF-α, which are all attenuated by SN in a dose- dependent manner.. SN exerts anticonvulsant and neuroprotective activity in PTZ kindling model of epilepsy. Disrupting the kindling acquisition, which inhibits NLRP1 inflammasome-mediated inflammatory process, might be involved in its effects.

Topics: Analysis of Variance; Animals; Anticonvulsants; CARD Signaling Adaptor Proteins; Caspase 1; Convulsants; Cytokines; Disease Models, Animal; Epilepsy; Kindling, Neurologic; Male; Maze Learning; Morphinans; Nerve Tissue Proteins; Pentylenetetrazole; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; RNA, Messenger

Radioreceptor-binding assay combined with autoradiography technique in the brain slices of rats was used to investigate cerebral areas related to electroconvulsive shock (ECS) and to analyze changes of opioid receptors of these areas in electroacupuncture (EA) anticonvulsion. The results from image processing and detection of optic density (O.D.) showed that repeated ECS resulted in an increase of opioid receptor densities in the caudate nucleus, hippocampus, habenulae nucleus and amygdala. In the group of EA plus ECS, however, the opioid receptor densities in the hippocampus, habenula nucleus and amygdala decreased as compared with that in ECS group. In addition, the receptor density in the caudate nucleus showed a decrease tendency. The results provided morphological evidence of the involvement of opioid receptors in these cerebral areas in the process of ECS and EA anticonvulsion.

Topics: Animals; Autoradiography; Brain; Electroacupuncture; Electroshock; Epilepsy; Etorphine; Female; Male; Morphinans; Rats; Receptors, Opioid