DISSIPATION OF CONTINGENT TOLERANCE TO THE ANTICONVULSANT EFFECT OF DIAZEPAM - EFFECT OF THE CRITERION RESPONSE

The effect of convulsive stimulations on the dissipation of tolerance to the anticonvulsant effect of diazepam was investigated using the ki ndled-convulsion model. Amygdala-kindled rats were rendered tolerant t o diazepam's anticonvulsant effect by 25 ''bidaily'' (one/48 h) diazep am injections (2.5 mg/kg), each followed 1 h later by a convulsive sti mulation. They were then divided into nine groups for the tolerance-di ssipation phase of the experiment. Of the nine groups, three received bidaily control handling for one trial, three trials, or seven trials; three received bidaily saline injections, each 1 h before a convulsiv e stimulation, for one, three, or seven trials; and three received bid aily diazepam injections, each 1 h after a convulsive stimulation, for one, three, or seven trials. Finally, each rat received a tolerance-r etention test (i.e., a diazepam injection followed I h later by a conv ulsive stimulation) 48 h after its last tolerance-dissipation trial. T he tolerance dissipated gradually but completely over the 4-, 8-, and 16-day test intervals in the rats that received a convulsive stimulati on before each injection during the tolerance-dissipation phase, wheth er they were injected with saline or diazepam; in contrast, tolerance did not dissipate in the rats that received saline injections but no s timulations. Remarkably, the discontinuance of the bidaily diazepam in jections, even for 16 days, was not sufficient to dissipate the tolera nce that had developed to diazepam's anticonvulsant effect; nor was th e continuation of the bidaily diazepam injections sufficient to keep t olerance from dissipating. The present findings support previous asser tions that the performance of the criterion response while undrugged i s the key factor in the dissipation of contingent drug tolerance; and they provide the first controlled demonstration of the time course of the dissipation.