Ameliorating effect of p-hydroxybenzyl alcohol on cycloheximide-induced impairment of passive avoidance response in rats: interactions with compounds acting at 5-HT1A and 5-HT2 receptors.

The effect of p-hydroxybenzyl alcohol (HBA) on cycloheximide (CXM)-induced impairment in the step-through passive avoidance task was investigated in rats and compared to the effect of the nootropic piracetam. HBA and piracetam significantly counteracted the CXM-induced shortening of retention latencies. The effect of HBA was a bell-shaped dose-response curve with a maximal effect of 5 mg/kg. The counteractive effect of HBA was not depressed by either scopolamine or mecamylamine. The serotonin (5-HT) releaser, p-chloroamphetamine, and presursor, 5-hydroxytryptophan, significantly antagonized the counteractive effect of HBA on the CXM-induced shortening of retention latencies. Furthermore, the counteractive effect was also inhibited by the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and the 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2 aminopropane [(+/-)-DOI], but potentiated by the 5-HT1 receptor antagonist (+/-)-pindolol and the 5-HT2 receptor antagonist ritanserin. There results suggest that the beneficial effect of HBA on CXM-induced impairment is amplified by treatment with serotonergic receptor antagonists but reduced by serotonergic 5-HT1A and 5-HT2 receptor agonists, and insensitive to cholinergic manipulations.