Contingent Tolerance to the Anticonvulsant Effects of Drugs on Kindled Convulsions

Abstract

At the Kindling 3 Conference in 1985, we reported that the development of tolerance to ethanol’s anticonvulsant effect on kindled convulsions elicited in rats by amygdalar stimulation is greatly influenced by the temporal relation between the administration of ethanol and the convulsive stimulation (18). We reported that substantial tolerance developed to ethanol’s anticonvulsant effect if the kindled rats were stimulated following each of five bidaily (once every 48 hr) intraperitoneal ethanol injections, but not if they were stimulated before each injection (see also 16). The fact that both groups of rats received the same exposure to ethanol and the same number of stimulations suggested that the critical factor in the development of the tolerance was the administration of convulsive stimulation during the periods of ethanol exposure. On the basis of this and similar observations (e.g, 13;17;20), we have proposed a theory of tolerance that emphasizes the idea that functional drug tolerance is a reaction to the expression of a drug’s effect rather than to the mere presence of the drug in the system (19). Although a drug’s effects are often an inevitable consequence of drug exposure, in some instances they may not be fully expressed unless the nervous system (or other target tissue) is involved in a specific pattern of neural activity during periods of drug exposure (cf., 4).