A genetic, physiological, and biochemical investigation of audiogenic seizures in rats

Abstract

Two kinds of audiogenic seizures are characteristic of the KM rat strain, selected by Krushinsky and Molodkina in Moscow in the 1940s. This strain is now approximately 100% sound sensitive. Diallel crosses have demonstrated the polygenic nature of this behavior, with most alleles for seizures being recessive. Myoclonic seizures which develop after several sound exposures are a special form of kindling, involving the limbic system. Selection for low and high rates of myoclonic seizures was successful. Several unique, physiological features of the audiogenic seizures in this rat strain are described, as well as data on RNA and protein synthesis inhibition effects on seizure formation.

Audiogenic Seizures - Biological Phenomenon and Experimental Model of Human Epilepsies

“…The heritability of audiogenic seizure in rats was no less simple issue. In KM rats the diallelic cross showed that AE heritability is polygenic with additive effects, and alleles determining the resistance to sound induced seizures were dominant (Romanova et al, 1993). The data on the genetic experiments in other AE rat strains are the following.…”

“…This selection was successful and the maximum selection effect in both new substrains was achieved in 4-5 generations. This made it possible to suggest that the predisposition for audiogenic kindling development is the oligogenic trait (Romanova et al, 1993). In mouse no data exist about the possibility to induce the audiogenic kindling.…”

“…Starting from the mid-50-s this new KM (for Krushinsky-Molodkina) strain had been extensively used as epilepsy model and model of catatonic state in pharmacological studies (Semiokhina et al, 2006). At that time authors avoided to describe the genetic aspect of the problem because scientific genetic investigation had been formally suppressed in Russia up to mid 60-s. Later the genetic study of AE inheritance had been performed (Romanova et al, 1993). In 1986-87 the inbreeding of KM strain was initiated, and up to the present the KM rat strain is maintained as inbred (more than 45 generations of inbreeding).…”

Long-term disease-modifying effect of the endocannabinoid agonist WIN55,212-2 in a rat model of audiogenic epilepsy

“…In KM rats audiogenic seizures can be evoked by acoustic stimulation [10]. Repetition of the seizures results in their prolongation, which is a reliable marker of the epileptogenic process called audiogenic kindling [11].…”

“…Repeated administration of the eCB agonist WIN55,212-2 (WIN) has been shown to retard electrical kindling [9] but the chronic treatment protocol complicates dissecting acute anticonvulsive and long-term anti-epileptogenic drug effects. The present study was designed to examine effects of WIN in a single-injection experiment in Krushinsky-Molodkina (KM) rats with genetic audiogenic epilepsy [10].…”