Tolerance to pentylentetrazol-induced convulsions and protection of cerebrovascular integrity by chronic nicotine

The authors' previous studies have shown that in nicotine-induced seizures sensitivity was decreased and blood-brain barrier (BBB) disruption was prevented as a consequence of nicotine pretreatment. This study aimed to investigate the possible protective actions of nicotine on cerebrovascular permeability and seizures induced by pentylentetrazol (PTZ) injection. Cerebrovascular effects of nicotine were evaluated by measuring the permeability changes of BBB using Evans-Blue (EB) dye and specific gravity (SG), which indicates brain water and protein content. The experiments were carried out on Wistar rats. Animals were randomly divided into two groups. Convulsions were induced by injection of PTZ (80 mg/kg i.v.) in rats either pretreated with nicotine daily with a low dose of 0.8 mg/kg day.for 21 days or injected with a single dose of 6 mg/kg mecamylamine. The same procedures were followed in control rats with the exception that they were injected only with saline. PTZ injection caused tonic-clonic convulsions and increased the EB dye leakage and specific gravity values in saline-injected control rat brains. Daily injection of nicotine lessened the intensity of seizures. These were accompanied by marked decreases in both the leakage of EB and brain water content. Acute administration of a nAChR antagonist mecamylamine significantly increased seizure latency and decreased the duration of seizures. Thereby, mecamylamine reduced the EB leakage and water content in most brain regions. These results indicate that development of tolerance to PTZ convulsions can be produced by chronic nicotine administration in rats. The mechanism for this effect currently needs clarification. Moreover, the data also suggest that cholinergic activity may account for occurrence of PTZ-induced convulsions

Nicotine improves learning and memory in rats: Morphological evidence for acetylcholine involvement

It has been suggested that nicotine improves rapid information processing (learning and memory) tasks. However, it is not clear which aspects of cognition actually underlie these improvements because relatively less attention has been given to nicotinic cholinergic systems compared to muscarinic systems. The authors therefore studied the effects of nicotine on the learning and memory performance by a step-through passive avoidance task. Nicotine (0.4 mg/kg) was administered s.c. single dose (acute group), once a day for 3 days (subchronic group) or 21 days (chronic group). Nicotine treated and control rats were trained in one trial learning step-through passive avoidance task, where retention latencies were carried out 1 h, 24 h, and 3 days after learning trial. Treatment with nicotine before training session prolonged the latencies significantly (p<.01). Control group, acute, subacute and chronic nicotine treatment groups showed latencies 4.75 +/- 0.6, 69.4 +/- 14, 116.2 +/- 30, and 118.5 +/- 23 s, respectively. In addition, to prove the actual contribution of nicotinic cholinergic system in improvement of learning and memory processing, histological methods that permit the visualization and quantification of ACh levels were used. Electron microscopic evaluation revealed increased numbers of Ach-containing vesicles especially in hippocampus in chronic nicotine-treated rats; although frontal and temporal cortex in addition to hippocampus showed increment in Ach vesicles in a lesser extent in all nicotine treatment groups. These results indicate that long-term nicotine treatment can be important for improving cognitive function in regard to increased cholinergic activity

Nitric oxide involvement in seizures elicited by pentylentetrazol and sex dependence

It has been known that susceptibility to some types of epilepsy is affected by sex. In addition, the role of NO in epileptogenesis is still unclear; NO has been suggested to be either an anticonvulsive or a proconvulsive agent. In an attempt to elucidate both the role of NO and sex differences in sensitivity to seizures, male and female Wistar rats were treated intraperitoneally (i.p.) by pentylentetrazol (PTZ)( 80 mg/kg) and by a nitric oxide synthase( NOS) inhibitor N-omega-nitro-L-arginine-mthylester(L-NAME)(50mg/kg) and a NO precursor sodium-nitroprusside (SNP) (2.5mg/kg)-applied 15 min. before PTZ injection. Latency, frequency, severity, and duration of generalized clonic and clonic-tonic convulsions were recorded. Furthermore, alterations in severity, latency, frequency, and duration of convulsions were observed to correlate with NO. Both sexes, injected with PTZ, showed repetitive seizure patterns. Seizures were found to be more severe in females. L-NAME and SNP pretreatment produced paradoxical effects on PTZ- induced seizures in both sexes. L-NAME completely prevented PTZ- induced seizures in male rats, whereas increased severity, frequency, duration, and significantly shortened the latency in female rats. Unexpectedly, SNP increased convulsion severity, frequency, duration, and shortened latencies in male, whereas it decreased convulsion severity, frequency, and duration and prolonged latency in females. These results indicate that endogenous NO is involved in the regulation of convulsive action suggesting a role depending on sex