Selective M1 muscarinic receptor antagonists disrupt memory consolidation of inhibitory avoidance in rats

The effect of three different M1 muscarinic antagonists, pirenzepine, biperiden, and trihexyphenidyl on memory consolidation was investigated. Rats were trained in a one-trial step-through inhibitory avoidance task and injected intraperitoneally immediately afterwards, either with pirenzepine, biperiden, or trihexyphenidyl (dose range from 0 to 16 mg/kg). The non-selective antimuscarinic compound scopolamine, was also administered for comparison. One day later, rats were tested for retention. Results show that biperiden, trihexyphenidyl and scopolamine produced a dose-dependent impairment of inhibitory avoidance consolidation, while pirenzepine had no effect. The amnestic state produced by biperiden and trihexyphenidyl was comparable to that observed after the administration of scopolamine. These results indicate that the selective blockade of the central M1 muscarinic receptors interfere with memory consolidation of inhibitory avoidance and suggest that this receptor subtype is critically involved in mnemonic functions.