Differences in vulnerability to nicotine-induced kindling between female and male periadolescent rats.

Rationale: It has recently been reported that chronic nicotine administration at subconvulsive doses causes seizures, a phenomenon referred to as kindling. Evidence points to the involvement of oxidative stress in pharmacological and electrical kindling, sex is known to influence the brain's response to nicotine.

Objectives: This study investigated the sex differences in vulnerability to nicotine-induced kindling and the involvement of oxidative stress in this phenomenon.

Methods: Male and female periadolescent Wistar rats received repeated injections of a subconvulsive dose of nicotine (hemisulfate salt; 2 mg/kg, i.p.) every weekday for up to 25 days. To better understand the influence of oxidative stress in nicotine kindling, the antioxidant vitamin E (200 and 400 mg/kg, p.o.) was administered prior to nicotine administration. The levels of gluthatione (GSH), superoxide dismutase (SOD) activity, and lipid peroxidation were determined in the hippocampus (HC), prefrontal cortex (PFC), and striatum.

Results: Female animals developed kindling more rapidly than male rats. In female rats, kindling was associated with decreases in antioxidant defenses, including GSH levels in the HC and striatum and SOD activity in the PFC and striatum, and increased lipid peroxidation in all brain areas studied. By contrast, male kindled animals presented only with a decrease in the GSH in the HC. Vitamin E prevented the occurrence of kindled seizures by 80 % and 75 % in male and female rats, respectively.

Conclusion: These novel findings indicate that female periadolescent rats develop nicotine-kindled seizures earlier than their male counterparts. Differences in the oxidative balance may be involved in this mechanism.