Post-Exposure Circulating Monoamine Alterations and Cerebral Cortex and Striatal Neuropathology Following Repeated Mkpurummiri Exposure in Female and Male Wistar Rats

Abstract

Illicit psychoactive street preparations represent a new neurotoxicological issue since their unclear and varied composition may result in consequences that cannot be predicted on the basis of their supposed drug identification. This study examined neurochemical and neuropathological modifications after repeated administration of mkpurummiri, a chemically characterised illicit street concoction from Southeast Nigeria. Male and female Wistar rats received mkpurummiri intraperitoneally once daily for 28 days at doses of 1, 2 or 5 mg/kg; control rats received vehicle. Histopathological changes and lesions were studied semiquantitatively in the cerebral cortex and striatum and circulating dopamine (DA), noradrenaline (NA) and serotonin (5-HT) were measured 24 h after the final injection. Mkpurummiri significantly affected all three circulating monoamines in both sexes (p < 0.001). Decreases in DA and NA and elevations in 5-HT were seen in an exposure-related manner. DA was decreased by 75.3% and 78.3%, NA by 47.1% and 47.2%, 5-HT was elevated by 446.6% and 589.1% in females and males, respectively, at 5 mg/kg. There was significant exposure × sex interactions for DA (p = 0.026) and 5-HT (p = 0.013). Histopathology demonstrated increasing neuronal degeneration and necrosis, reactive cellular alterations and vascular/neurovascular abnormalities in cerebral cortex and striatum. These findings provide complementary neurochemical and morphological evidence of neurotoxicity related with mkpurummiri and show biological changes observable 24 h after final exposure.