Tolerance to the depressant effects of diazepam in the drug discrimination paradigm.
Seven groups of rats (n = 35) were run in operant drug experiments. All groups were trained on a Fixed Ratio 10 schedule to discriminate diazepam from saline. Two groups (n = 7, n = 6), after extensive drug discrimination training (doses of 2.0 and 3.0 mg/kg diazepam), were submitted to generalization experiments with various doses of the training drug. Two additional groups, (n = 6, n = 8) in the initial phase of drug discrimination, were trained on intermediate and high doses of diazepam (i.e., 5.0 and 10.0 mg/kg). The development of tolerance to the depressant effects of diazepam for these two groups was compared to the low dose sophisticated rats. Of the above-mentioned groups, two groups were given tests after a waiting period in drug discrimination training. In this test the two groups were compared to an additional group (n = 8) in its initial phases of drug discrimination training. The results show that a large number of low doses (i.e., doses below 3.0 mg/kg) is not able to induce any tolerance to the depressant effects of diazepam in this particular paradigm. Intermediate doses of diazepam (i.e., 3.0 mg/kg), administered in a large number, induced some tolerance to the depressant effects, while another intermediate dose (5.0 mg/kg) and a high dose (10.0 mg/kg) rapidly induced a significant tolerance. Once developed, the tolerance persisted for 51 days.
D000704:Analysis of Variance; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D003864:Depression, Chemical; D003975:Diazepam / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects*; D004361:Drug Tolerance; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D003975:Diazepam