Spatiotemporal analysis of fos expression associated with cocaine- and PTZ-induced seizures in prenatally cocaine-treated rats

We previously reported that prenatal cocaine exposure (40 mg/kg s.c., E10-E 20) increased susceptibility to convulsant-induced seizures later in life, with female rats becoming more sensitive to seizures induced by cocaine and pentylenetetrazol (PTZ), and males more sensitive to PTZ-induced seizures (Snyder-Keller and Keller, 1995, 2000). In order to determine the locus of enhanced seizure susceptibility in the brains of prenatally cocaine-treated rats, we examined the distribution and density of Fos-immunoreactive cells after cocaine- and PTZ-induced seizures in mature rats. Subconvulsive coca ine doses induced c-fos in cortical areas as well as densely dopamine-inner vated regions such as striatum and nucleus accumbens. Following cocaine-ind uced seizures, intense c-fos induction was observed in piriform cortex, amy gdala, and hippocampus. Quantification of the number of Fos-immunoreactive cells in the brains of prenatally cocaine-treated versus prenatally saline- treated rats revealed differences in piriform cortex and amygdala that were indicative of a lower threshold in prenatally cocaine-treated female rats. Following PTZ-induced seizures, the same pattern of limbic structures were recruited with increasing seizure severity. Only females exhibited changes in the number of Fos-immunoreactive cells as a result of prenatal cocaine treatment. Pretreatment with the noncompetitive NMDA antagonist MK-801 bloc ked both cocaine- and PTZ-induced seizures, and Fos expression in limbic ar eas was also blocked. The dopamine D1 antagonist SCH 23390 blocked cocaine- induced seizures and associated c-fos induction, but not PTZ-induced seizur es or Fos. Examination of the pattern of Fos expression at 15-20 min postse izure revealed that the initial site of c-fos induction associated with PTZ -induced seizures appeared to be the piriform cortex, whereas cocaine-induc ed seizures induced early expression in both piriform cortex and lateral am ygdala. These findings suggest that neural alterations residing in the piri form cortex and amygdala are likely to account for the increased seizure su sceptibility of prenatally cocaine-treated rats. (C) 2001 Academic Press.