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NMDA receptor antagonism disrupts acquisition and retention of the context preexposure facilitation effect in adolescent rats.
Behav Brain Res. 2016 Mar 15; 301:168-77.BB

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+Show Affiliations

Department of Psychological and Brain Sciences, University of Delaware, Newark, DE 19716, United States.Department of Psychological and Brain Sciences, University of Delaware, Newark, DE 19716, United States.Department of Psychological and Brain Sciences, University of Delaware, Newark, DE 19716, United States.Department of Psychological and Brain Sciences, University of Delaware, Newark, DE 19716, United States. Electronic address: Stanton@udel.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

26711910

Citation

Heroux, Nicholas A., et al. "NMDA Receptor Antagonism Disrupts Acquisition and Retention of the Context Preexposure Facilitation Effect in Adolescent Rats." Behavioural Brain Research, vol. 301, 2016, pp. 168-77.
Heroux NA, Robinson-Drummer PA, Rosen JB, et al. NMDA receptor antagonism disrupts acquisition and retention of the context preexposure facilitation effect in adolescent rats. Behav Brain Res. 2016;301:168-77.
Heroux, N. A., Robinson-Drummer, P. A., Rosen, J. B., & Stanton, M. E. (2016). NMDA receptor antagonism disrupts acquisition and retention of the context preexposure facilitation effect in adolescent rats. Behavioural Brain Research, 301, 168-77. https://doi.org/10.1016/j.bbr.2015.12.025
Heroux NA, et al. NMDA Receptor Antagonism Disrupts Acquisition and Retention of the Context Preexposure Facilitation Effect in Adolescent Rats. Behav Brain Res. 2016 Mar 15;301:168-77. PubMed PMID: 26711910.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NMDA receptor antagonism disrupts acquisition and retention of the context preexposure facilitation effect in adolescent rats. AU - Heroux,Nicholas A, AU - Robinson-Drummer,Patrese A, AU - Rosen,Jeffrey B, AU - Stanton,Mark E, Y1 - 2015/12/19/ PY - 2015/10/09/received PY - 2015/12/06/revised PY - 2015/12/15/accepted PY - 2015/12/30/entrez PY - 2015/12/30/pubmed PY - 2016/10/21/medline KW - CPFE KW - Dose-response NMDA receptor involvement in the CPFE KW - NMDA receptors KW - Postshock KW - Retention KW - Systemic MK-801 SP - 168 EP - 77 JF - Behavioural brain research JO - Behav Brain Res VL - 301 N2 - 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. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/26711910/NMDA_receptor_antagonism_disrupts_acquisition_and_retention_of_the_context_preexposure_facilitation_effect_in_adolescent_rats_ DB - PRIME DP - Unbound Medicine ER -