The effect of hyperglycemia on cocaine neurotoxicity and death in mice.

Abstract

Cocaine toxicity frequently manifests as seizures and status epilepticus. Frequently, dextrose is administered to patients with cocaine-induced seizures. The objective of this study was to examine the effect of pre-existing hyperglycemia on cocaine neurotoxicity and death in mice. Swiss albino mice received intraperitoneal dextrose at a dose of 1 g/kg (12.5%) (hyperglycemic group, n = 98). The euglycemic group (n = 98) received an equal volume of 0.9% saline. After 60 minutes, all the animals received intraperitoneal cocaine at a dose of 90 mg/kg. The times to onset of ataxia, seizure, and death were recorded in seconds. Times to events were compared using a Kaplan-Meier method and results were compared using the logrank test. The overall percentage outcomes were compared using chi-square. The ataxia rates (hyperglycemic 97%, euglycemic 97%, chi(2) = 0, p = 1), seizure rates (hyperglycemic 85%, euglycemic 82%, chi(2) = 0.292, p = 0.589), and survival rates (hyperglycemic 62%, euglycemic 51%, chi(2) = 0.2514, p = 0.113) were similar between the groups. The survival following a seizure was significantly higher in the hyperglycemic group (hyperglycemic 57%, euglycemic 41%, chi(2) = 4.439, p = 0.035). The median ataxia time was earlier in the hyperglycemic group (190 sec) than in the euglycemic group (166 sec) (p = 0.031). Seizures occurred no earlier in the hyperglycemic group (331 sec) than in the euglycemic group (342 sec) (p = 0.207). Survival times were not different for the hyperglycemic group (9,133 sec) and the euglycemic group (7,593 sec) (p = 0.394). Survival times following seizures were not different for the hyperglycemic group (8,095 sec) and the euglycemic group (5,816 sec) (p = 0.0752). In mice with pre-existing hyperglycemia, ataxia occurred earlier and survival following cocaine-induced seizures was longer than for euglycemic mice. No significant difference in the overall percentage of seizures and death was detected. Pre-existing hyperglycemia had minimal effect on worsening cocaine toxicity in mice.