The effect of nicotine pretreatment on the blood-brain barrier permeability in nicotine-induced seizures

Abstract

Nicotine is a toxic substance which because of its lipid solubility can cross the blood brain barrier. It has several different actions in the CNS; one of which is neuroexcitation, where it can result in seizure activity. Based on the observations that nicotine pretreatment ameliorated blood flow and glucose utilisation in caudate putamen on rats whose mesostriatal dopamine system had been cut and that nicotine pretreatment rendered animals less susceptible to nicotine induced seizures than saline administered controls, we conducted this set of experiments where we investigated the protective effect of nicotine pretreatment on the BBB permeability in nicotine induced seizures. Administration of saline or subseizure producing dose of nicotine (1 mg/kg i.p.) was followed by seizure producing doses of nicotine (2, 5 or 8 mg/kg, i. p.). Intravenous technique was used to calculate the unidirectional blood to brain transfer constant (Kin) for six different brain regions, with [H-3] alpha-AIB as a tracer. Mean Kin in brains of all acute nicotine groups (2, 5 or 8 mg/kg) increased by 83.94%, 182.6% and 265% respectively. Twenty one days chronic nicotine pretreatment prevented the rise in Kin AIB to 2 mg/kg acute nicotine and partially ameliorated the disturbed BBB to 5 and 8 mg/kg.