Administration of muscarinic antagonists induce changes in passive avoidance learning and in synaptic transmission in the CA1 area of the hippocampus

Muscarinic acetylcholine receptors (mAChR) are known to be related to learning and memory processes. Inactivation of mAChR by cholinergic antagonists have been shown to produce amnesia in a variety of behavioral tasks. In this study, we investigated the role of M1 and M2 AChR on passive avoidance learning and plasticity of synapses formed by Schaffer collaterals in freely moving rats. Experiments were performed using Wistar male rats. Seven days before testing, a recording electrode was lowered in the CA1 region under chloral hydrate anaesthesia to record the field excitatory postsynaptic potential (fEPSP) in response to Schaffer collateral stimulation. Selective M2 receptor antagonists methoctramine and selective M1 receptors antagonist pirenzepine were intraperitoneally injected immediately after training. The effects on memory retention were examined using passive avoidance training. We measured latency of the first entry into a dark compartment of the chamber. fEPSP amplitude and slope ratio were measured before shock presentation, 90 min after the shock, and 24 hour after the shock. Methoctramine significantly impaired behavior in the passive avoidance test but pirenzepine did not induce any changes compared to control. Our results showed that pirenzepine but not methoctramine supressed the amplitude of fEPSPs. On the other hand, intracerebroventricular methoctramine administration impaired passive avoidance learning and increased the amplitude of fEPSP.