title: NMDA receptor antagonism disrupts acquisition and retention of the context preexposure facilitation effect in adolescent rats.
abstract: 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 0.1mg/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 24h later. Experiment 3 showed that expression of contextual fear via a 24h 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 0.1mg/kg MK-801 disrupted both postshock and retention test freezing while lower pre-training doses of MK-801 (0.025 or 0.05mg/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.
authors.affiliation: Department of Psychological and Brain Sciences, University of Delaware, Newark, DE 19716, United States.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Heroux
authors.affiliation: Department of Psychological and Brain Sciences, University of Delaware, Newark, DE 19716, United States.
authors.forename: Patrese A
authors.initials: PA
authors.lastname: Robinson-Drummer
authors.affiliation: Department of Psychological and Brain Sciences, University of Delaware, Newark, DE 19716, United States.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Rosen
authors.affiliation: Department of Psychological and Brain Sciences, University of Delaware, Newark, DE 19716, United States. Electronic address: Stanton@udel.edu.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Stanton
mesh_terms: D000818:Animals; D001245:Association Learning / Q000187:drug effects* / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005239:Fear / Q000187:drug effects / Q000502:physiology; D005260:Female; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D009483:Neuropsychological Tests; D011897:Random Allocation; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate
keywords: CPFE; Dose-response NMDA receptor involvement in the CPFE; NMDA receptors; Postshock; Retention; Systemic MK-801