The effects of adolescent cannabinoid exposure on seizure susceptibility and lethality in adult male rats

There is substantial evidence in rodent models that chronic exposure to cannabinoids during adolescence can alter the development of neurobiological systems that are implicated in regulating brain activity and seizure. The current study explored whether adolescent cannabinoid treatment affects subsequent, adult seizure susceptibility. Sixty male Wistar Kyoto rats were treated with either the synthetic cannabinoid, CP 55,940 (0.4 mg/kg, one treatment per day), or vehicle between 35 and 45 days old. Subjects were then allowed to mature to adulthood. At 68-69 days of age, subjects were tested for seizure susceptibility using the pro-convulsant, pentylenetetrazol (PTZ). Subjects received an acute injection of either 35 mg/kg or 50 mg/kg PTZ immediately prior to a 30-min behavioral seizure test PTZ doses were chosen to produce low-to-moderate levels of seizure activity in control subjects. There were no significant differences between treated and control subjects in: latency to first seizure, mean seizure severity, percentage who displayed any seizure activity, percentage who displayed clonic seizure, or percentage who displayed tonic-clonic seizure. However, CP 55,940-treated subjects had a higher mortality rate compared to controls at both PTZ doses, suggesting that adolescent cannabinoid exposure may increase the lethality of severe seizures experienced in adulthood. (C) 2015 Elsevier Inc. All rights reserved.