Hippocampus-dependent fear conditioning is not sensitized by muscarinic receptor activation following systemic injection of pilocarpine

The regulation of muscarinic acetylcholine receptors (mAChR) critically influences emotional outcomes. Previous researches indicate that a single systemic injection of pilocarpine – a mAChR agonist – displays long-term defensive behaviors in rats evaluated in distinct unconditioned tests up to 3 months following treatment. However, it is not clear whether these effects share underlying behavioral phenotypes involved in conditioned responses. With this in mind, we examined whether mAChR activation modulates contextual fear conditioning (CFC) and/or hippocampal synaptic plasticity. Adult male Wistar rats were injected with pilocarpine (150 mg/kg) and behaviorally evaluated in the CFC test or followed by synaptic plasticity (LTP/LTD) investigation in CA1 stratum radiatum of hippocampal slices. There was no difference between groups in the quantification of freezing behavior during the test period (24 h after treatment) besides a decrease of freezing 1 month later. Similarly, no changes were observed in rats conditioned 24 h later and tested 1 month after. Synaptic plasticity investigation following short- or long-term treatment revealed no differences between control and treated subjects. In summary, our results show that hippocampus-dependent fear behavior and memory consolidation mediated by hippocampal cholinergic inputs are not sensitive to activation of mAChR by a systemic nonconvulsant dose of pilocarpine. Therefore, we suggest that the long-term defensive behaviors and anxiogenic-like features displayed by pilocarpine observed in rats are mediated by different underlying mechanisms and or set of synapses.