Roles of hippocampal GABAA and muscarinic receptors in consolidation of context memory and context–shock association in contextual fear conditioning: A double dissociation study

Contextual fear conditioning involves forming a context representation and associating it to a shock, both of which involved the dorsal hippocampus (DH) according to our recent findings. This study tested further whether the two processes may rely on different neurotransmitter systems in the DH. Male Wistar rats with cannula implanted into the DH were subjected to a two-phase training paradigm of contextual fear conditioning to separate context learning from context–shock association in two consecutive days. Immediately after each training phase, different groups of rats received bilateral intra-DH infusion of the GABAA agonist muscimol, 5HT1A agonist 8-OH-DPAT, NMDA antagonist APV or muscarinic antagonist scopolamine at various doses. On the third day, freezing behavior was tested in the conditioning context. Results showed that intra-DH infusion of muscimol impaired conditioned freezing only if it was given after context learning. In contrast, scopolamine impaired conditioned freezing only if it was given after context–shock training. Posttraining infusion of 8-OH-DPAT or APV had no effect on conditioned freezing when the drug was given at either phase. These results showed double dissociation for the hippocampal GABAergic and cholinergic systems in memory consolidation of contextual fear conditioning: forming context memory required deactivation of the GABAA receptors, while forming context–shock memory involved activation of the muscarinic receptors.

► Context learning and shock learning were dissociated in contextual fear conditioning.
► Intra-hippocampal drug infusion after context or shock learning had distinct effects.
► Muscimol given after context learning impaired formation of context memory.
► Scopolamine given after shock learning impaired formation of context–shock memory.
► Context leaning and shock learning involve different transmitters in the hippocampus.