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Extinction in preweanling rats does not involve NMDA receptors.
Neurobiol Learn Mem. 2010 Sep; 94(2):176-82.NL

Abstract

Past research has shown that the N-methyl-d-aspartate receptor (NMDAr) is critically involved in the extinction of learned fear in adult rats with NMDAr antagonists impairing extinction retention and NMDAr agonists enhancing it. In the present study we examined the effects of the NMDAr antagonist MK-801 on extinction in the developing rat. In Experiment 1, rats were given pairings of a white-noise conditioned stimulus (CS) and a shock unconditioned stimulus (US) on postnatal day (P)16. An extinction session, where the CS was presented without the US, occurred on P17 or P24. Prior to extinction rats were injected with MK-801 or saline. All rats were tested for fear of the CS on P25, while drug free. Saline-treated rats exhibited good retention of extinction whether they were extinguished at P17 or P25. Rats treated with MK-801 exhibited impaired extinction retention but only if extinction occurred on P24. These findings show that extinction is NMDAr-dependent at P24 but NMDAr-independent at P17. Experiment 2 further examined the involvement of NMDA receptors in extinction at different stages of development by taking advantage of a finding from several recent studies on re-extinction. These studies have shown, in adult rats, a transition from NMDAr-dependent extinction to NMDAr-independent re-extinction. That is, if rats are trained, extinguished, re-trained to the same CS, and then extinguished again (i.e., re-extinction), then NMDA receptors are not required for extinction the second time. In Experiment 2, rats were trained to fear the CS at P16; this fear was extinguished at either P17 or P24. All rats were then re-trained to fear the CS at P25, re-extinguished at P26, and tested at P27. Prior to re-extinction, rats were injected with MK-801 or saline. Rats initially extinguished at P24, an age where NMDA receptors are involved in extinction, exhibited the transition to an NMDAr-independent re-extinction process. In contrast, rats initially extinguished at P17, an age where NMDA receptors are not involved in extinction, did not (i.e., these rats still exhibited an impairment in extinction retention if given MK-801 prior to re-extinction). Taken together, these findings demonstrate that a qualitatively different system mediates extinction early in life.

Authors+Show Affiliations

School of Psychology, University of New South Wales, Anzac Parade, Kensington, Sydney, New South Wales 2052, Australia. kimjeehyun@ymail.comNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20472087

Citation

Kim, Jee Hyun, and Rick Richardson. "Extinction in Preweanling Rats Does Not Involve NMDA Receptors." Neurobiology of Learning and Memory, vol. 94, no. 2, 2010, pp. 176-82.
Kim JH, Richardson R. Extinction in preweanling rats does not involve NMDA receptors. Neurobiol Learn Mem. 2010;94(2):176-82.
Kim, J. H., & Richardson, R. (2010). Extinction in preweanling rats does not involve NMDA receptors. Neurobiology of Learning and Memory, 94(2), 176-82. https://doi.org/10.1016/j.nlm.2010.05.004
Kim JH, Richardson R. Extinction in Preweanling Rats Does Not Involve NMDA Receptors. Neurobiol Learn Mem. 2010;94(2):176-82. PubMed PMID: 20472087.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Extinction in preweanling rats does not involve NMDA receptors. AU - Kim,Jee Hyun, AU - Richardson,Rick, Y1 - 2010/05/21/ PY - 2010/01/15/received PY - 2010/05/06/revised PY - 2010/05/10/accepted PY - 2010/5/18/entrez PY - 2010/5/18/pubmed PY - 2010/12/14/medline SP - 176 EP - 82 JF - Neurobiology of learning and memory JO - Neurobiol Learn Mem VL - 94 IS - 2 N2 - Past research has shown that the N-methyl-d-aspartate receptor (NMDAr) is critically involved in the extinction of learned fear in adult rats with NMDAr antagonists impairing extinction retention and NMDAr agonists enhancing it. In the present study we examined the effects of the NMDAr antagonist MK-801 on extinction in the developing rat. In Experiment 1, rats were given pairings of a white-noise conditioned stimulus (CS) and a shock unconditioned stimulus (US) on postnatal day (P)16. An extinction session, where the CS was presented without the US, occurred on P17 or P24. Prior to extinction rats were injected with MK-801 or saline. All rats were tested for fear of the CS on P25, while drug free. Saline-treated rats exhibited good retention of extinction whether they were extinguished at P17 or P25. Rats treated with MK-801 exhibited impaired extinction retention but only if extinction occurred on P24. These findings show that extinction is NMDAr-dependent at P24 but NMDAr-independent at P17. Experiment 2 further examined the involvement of NMDA receptors in extinction at different stages of development by taking advantage of a finding from several recent studies on re-extinction. These studies have shown, in adult rats, a transition from NMDAr-dependent extinction to NMDAr-independent re-extinction. That is, if rats are trained, extinguished, re-trained to the same CS, and then extinguished again (i.e., re-extinction), then NMDA receptors are not required for extinction the second time. In Experiment 2, rats were trained to fear the CS at P16; this fear was extinguished at either P17 or P24. All rats were then re-trained to fear the CS at P25, re-extinguished at P26, and tested at P27. Prior to re-extinction, rats were injected with MK-801 or saline. Rats initially extinguished at P24, an age where NMDA receptors are involved in extinction, exhibited the transition to an NMDAr-independent re-extinction process. In contrast, rats initially extinguished at P17, an age where NMDA receptors are not involved in extinction, did not (i.e., these rats still exhibited an impairment in extinction retention if given MK-801 prior to re-extinction). Taken together, these findings demonstrate that a qualitatively different system mediates extinction early in life. SN - 1095-9564 UR - https://www.unboundmedicine.com/medline/citation/20472087/Extinction_in_preweanling_rats_does_not_involve_NMDA_receptors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1074-7427(10)00087-0 DB - PRIME DP - Unbound Medicine ER -