Muscarinic toxin selective for m4 receptors impairs memory in the rat

The selectivity of the muscarinic toxin MT3 from green mamba snake venom was corroborated by inhibition of the binding of [3H]NMS, a classical muscarinic radioligand, to native and cloned muscarinic receptors, showing 214-fold higher affinity for m4 than for m1 subtype, without significant binding to the others. The highest concentrations of MT3 sites (putative m4 receptors) in the rat brain were found in striatum and olfactory tubercle, intermediate concentration in dentate gyrus and CA1, and lower but still conspicuous levels in CA3 and frontal cortex. MT3 caused retrograde amnesia of an inhibitory avoidance task, when injected into the dorsal hippocampus of rats after training, suggesting a positive role of these MT3 sensitive sites, which are probably m4 muscarinic receptors, in memory consolidation of this task.