Differential audiogenic seizure sensitization by selective unilateral substantia nigra lesions in resistant Wistar rats

Abstract

Evaluation of the participation of different substantia nigra sites in the sensitization of resistant (R) animals to audiogenic seizures (AS) , was performed after series of small (5 mC; n = 28), medium (10 mC; n = 57) and large (15 mC; 3 points of 5 mC each, n = 19) unilateral electrolytic lesions of the substantia nigra (SN) in R rats. Animals were evaluated at 5, 10, 15, and 30 days post surgery and behavior was measured by a neuroethological method. Small unilateral lesions induced AS susceptibility in 14% R animals with 3% of them displaying tonic-clonic AS. Medium sized lesions induced AS susceptibility in 50% of the animals with 18% of these exhibiting tonic-clonic seizures similar to those displayed by naturally susceptible (S) animals, but with predominance of wild running (gyri, jumping and atonic falling) contralateral to the lesioned SN. AS severity was significantly higher at day 5 postsurgery, decreasing at days 10, 15 and 30. Large unilateral lesions destroying the entire SN failed to cause tonic-clonic seizures although wild running occurred in 10% of the animals. Bilateral large SN lesions (15 mC; n = 24) did not modify AS severity in S animals, but only induced a statistically significant increase in the AS latency. The present data suggest: (i) AS severity after SN lesions is not a linear function of the lesion size; (ii) functionally different and antagonistic AS related substrates may exist in the SN; (iii) neurochemical and hodological characterization of these areas should be important for a better understanding of their role in AS.