A single prior undrugged exposure to the four-plate test reduces punished responding on retest at intervals ranging from 24 h to 42 days. Furthermore, prior experience attenuates the anxiolytic response to the benzodiazepines diazepam (0.25 to 2 mg/kg) and lorazepam (0.5 to 4 mg/kg). The result was first discussed in term of "one trial tolerance." The anxiety baseline was increased during the retest, which counteracted the anxiolytic action of benzodiazepines. To ascertain if memory processes are also implicated, the cholinergic drugs scopolamine and oxotremorine were used. Additional experiments with the GABAergic inverse agonist FG7142 and with the 5-HT1A receptor agonist 8-OH-DPAT were also performed. Administration of scopolamine and 8-OH-DPAT-induced weak impairment of memory, when administered before the second trial, but no effect was seen with cognition enhancing agents.