Cholinergic effects on fear conditioning II: nicotinic and muscarinic modulations of atropine-induced disruption of the degraded contingency effect.

In a companion study (Carnicella et al., 2005), we showed that the muscarinic antagonist atropine, when administered after extensive training during both conditioning and testing, affected neither cued nor contextual fear memories when both of them did not compete for the control of the overt behaviour. In contrast, atropine altered the degraded contingency effect (DCE), that is, the processes by which contextual fear memory competes with the cued one for the control of the conditioned response. Atropine-induced disruption of the DCE was fully reversed by the administration of the anticholinesterase inhibitor physostigmine, which suggests a direct cholinergic implication. The present series of experiments was conducted in order to define more precisely the involvement of the cholinergic system in such an effect. Oxotremorine (0.0, 0.0075, 0.015, or 0.03 mg/kg), pilocarpine (0.0, 0.3, 1, or 3 mg/kg), xanomeline (0.0, 2.5, 5.0, 10.0 or 20.0 mg/kg) and nicotine (0.0, 0.1, 0.2, or 0.4 mg/kg) were tested for reversal of the atropine-induced alteration of the DCE. Oxotremorine and pilocarpine did not reverse the atropine-induced alteration of the DCE. In contrast, xanomeline and nicotine reversed the effect of atropine on the DCE. The present series of experiments reveals complex pharmacological interactions within the cholinergic system when cued and contextual fear memories interact. Results are discussed in this connection and with regard to the relation between the properties of cholinergic agonists and their therapeutic values.