Genetic Differences in the Development of Physical Dependence on Pentobarbital in Four Inbred Strains of Rat

Abstract

Fischer 344 (F344), Lewis (LEW), spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats were chronically fed food containing pentobarbital on an escalating drug dosage schedule over a period of 47 days. During treatment, the growth curve in LEW, SHR and WKY rats was suppressed as compared with the respective controls. Motor incoordination was evaluated by a rotarod performance test. The ranking of the motor incoordination was as follows: WKY>>j LEW>SHR>F344. After substitution of normal food for the pentobarbital-admixed food, various signs of pentobarbital withdrawal occurred. The withdrawal signs from pentobarbital in F344, LEW and SHR rats were mild as compared with those in WKY rats. The order of the severity of withdrawal signs in four inbred strains was parallel to that for motor incoordination. These results suggest that the differences between strains in withdrawal can be attributed to differences in the degree of chronic CNS depression produced by pentobarbital.