NMDA receptor antagonism disrupts acquisition and retention of the context preexposure facilitation effect in adolescent rats

• In adolescent rats, the context preexposure facilitation effect depends on NMDA receptor activation on either the preexposure or training day but not the testing day.
• These effects appear during fear acquisition (post-shock freezing) and 24-h retention.
• NMDA receptor activation following preexposure has a partial effect, and following training, no effect on the CPFE in adolescent rats.
• Acquisition (post-shock freezing) vs. 24-h retention show different dose-response functions. Lower doses of NMDA antagonists disrupt 24-h retention but not post-shock freezing.

The context preexposure facilitation effect (CPFE) is a contextual fear conditioning paradigm in which learning about the context, acquiring the context-shock association, and retrieving/expressing contextual fear are temporally dissociated. The current study investigated the involvement of NMDA receptors in contextual fear acquisition, retention, and expression across all phases of the CPFE in adolescent rats. In Experiment 1 systemic injections of 0.1 mg/kg MK-801, a non-competitive NMDA receptor antagonist, given before multiple context preexposure disrupted the acquisition of a context representation. In Experiment 2, pre-training MK-801 disrupted both immediate acquisition of contextual fear measured by postshock freezing, as well as retention test freezing 24 h later. Experiment 3 showed that expression of contextual fear via a 24 h retention freezing test does not depend on NMDA receptors, indicating that MK-801 disrupts learning rather than performance of freezing behavior. In Experiment 4, consolidation of contextual information was partially disrupted by post-preexposure MK-801 whereas consolidation of contextual fear was not disrupted by post-training MK-801. Finally, Experiment 5 employed a dose-response design and found that a pre-training dose of 0.1 mg/kg MK-801 disrupted both postshock and retention test freezing while lower pre-training doses of MK-801 (0.025 or 0.05 mg/kg) only disrupted retention freezing. This is the first study to distinguish the role of NMDA receptors in acquisition (post-shock freezing), retention, expression, and consolidation of context vs. context-shock learning using the CPFE paradigm in adolescent rats. The findings provide a foundation for similar developmental studies examining these effects from early ontogeny through adulthood.