Naloxone improves impairment of spatial performance induced by pentylenetetrazol kindling in rats.

The role of endogenous opioid peptides in impairment of spatial performance due to epileptogenesis was examined. Animals were kindled by repeated injections of pentylenetetrazol (PTZ) (40 mg/kg, i.p.) in the presence or absence of the opioid receptor antagonist naloxone. Naloxone in different doses (1, 5 and 10 mg/kg, i.p.) was applied 30 min before each PTZ injection. Behavioral testing was assessed 24 h and 10 days after the last injection in separate groups of animals using Morris water maze. Our results showed that PTZ-induced kindling produced a significant impairment of spatial learning and memory as compared with controls and this effect was not due to the aftereffect of repeated seizures. Naloxone pretreatment in the course of kindling had no effect on seizures development, however it caused an improvement of spatial learning and memory performance in kindled rats. It is likely that the long-lasting changes in neuronal responsiveness associated with kindling led to a defect in the processing of spatial information. These data suggest that endogenous opioid peptides released in the hippocampus during kindling are at least in part responsible for impairment of spatial performance in kindled animals.

Effect of prenatal pentylenetetrazol-induced kindling on learning and memory of male offspring.

Current data concerning the effects of maternal seizure during pregnancy on newborns are limited. This study was carried out to investigate the effect of prenatal pentylenetetrazol (PTZ)-induced kindling on learning and memory of offspring. Female Wistar rats were kindled with i.p. injections of 25 mg/kg of PTZ on day 13 of their pregnancy. The spatial performance and passive avoidance learning of pups were tested at 7 weeks and 12 weeks of age using Morris water maze (MWM) task and shuttle-box apparatus, respectively. We found, for the first time, that prenatal exposure to maternal seizure induced by PTZ leads to a significant impairment of learning and memory. In addition, the number of live birth was significantly lower in kindled rats compared to control. In MWM studies, the young offspring of kindled rats had poor spatial learning ability. The frequent tonic-clonic seizures in pregnancy was also associated with a poor memory as evidenced by decrease in distance swam in the target quadrant by the offspring of the kindled mother in the adulthood. Data obtained from shuttle-box studies showed that retention latencies of pups born to kindled dams were significantly reduced compared to those born to control dams. The hippocampus, amygdala and frontal cortex are very important for memory consolidation and our data suggest that subsequent developmental events are not sufficient to overcome the adverse effects of prenatal exposure to maternal seizures to these regions of the brain. These observations may have clinical implications for cognitive and memory dysfunction associated with epilepsy during pregnancy.