Effect of repeated seizure experiences on tyrosine hydroxylase immunoreactivities in the brain of genetically epilepsy-prone rats

The genetically epilepsy-prone rat (GEPR) is a model of generalized tonic/c lonic epilepsy, and has functional noradrenergic deficiencies that act as p artial determinants for the seizure predisposition and expression, The pres ent study investigated the effect of repeated seizure experiences by acoust ic stimulation (110 dB, 10 times) on the immunoreactivities of tyrosine hyd roxylase (TH), a rate-determining enzyme in the synthesis of norepinephrine , in brain regions of GEPRs. TH immunoreactivity in locus coeruleus, the ma jor noradrenergic nucleus in brain, was lower in GEPRs than control Sprague -Dawley rats. It was also decreased in several regions including inferior c olliculus of GEPRs. Repeated experiences of audiogenic seizures further dec reased TH immunoreactivities in locus coeruleus and inferior colliculus of GEPRs. The results from the present study suggest that the lower immunoreac tivities of TH in locus coeruleus and inferior colliculus contribute, at le ast in part, to the noradrenergic deficits in GEPRs, and repeated seizure e xperiences further intensified these noradrenergic deficits, which may be r elated to the altered seizure expression by repetitive audiogenic seizure i n GEPRs. (C) 2001 Elsevier Science Inc.