Elucidating the mechanisms of fear extinction in developing animals: a special case of NMDA receptor-independent extinction in adolescent rats

被引:6
作者
Bisby, Madelyne A. [1 ]
Baker, Kathryn D. [1 ]
Richardson, Rick [1 ]
机构
[1] UNSW Sydney, Sch Psychol, Sydney, NSW 2052, Australia
基金
澳大利亚国家健康与医学研究理事会; 澳大利亚研究理事会; 英国医学研究理事会;
关键词
NICOTINIC ACETYLCHOLINE-RECEPTOR; VENTROMEDIAL PREFRONTAL CORTEX; ENDOCANNABINOID SYSTEM; POTENTIATED STARTLE; LEARNED FEAR; AMYGDALA; MK-801; MEMORY; EXPRESSION; TERM;
D O I
10.1101/lm.047209.117
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
NMDA receptors (NMDARs) are considered critical for the consolidation of extinction but recent work challenges this assumption. Namely, NMDARs are not required for extinction retention in infant rats as well as when extinction training occurs for a second time (i.e., reextinction) in adult rats. In this study, a possible third instance of NMDAR-independent extinction was tested. Although adolescents typically exhibit impaired extinction retention, rats that are conditioned as juveniles and then given extinction training as adolescents (JuvCond-AdolesExt) have good extinction retention. Unexpectedly, this good extinction retention is not associated with an up-regulation of a synaptic plasticity marker in the medial prefrontal cortex, a region implicated in extinction consolidation. In the current study, rats received either the noncompetitive NMDAR antagonist MK801 (0.1 mg/kg, s.c.) or saline before extinction training. In several experiments, rats conditioned and extinguished as juveniles, adolescents, or adults exhibited impaired extinction retention after MK801 compared to saline, but this effect was not observed in JuvCond-AdolesExt rats. Further experiments ruled out several alternative explanations for why NMDAR antagonism did not affect extinction retention in adolescents extinguishing fear learned as a juvenile. These results illustrate yet another circumstance in which NMDARs are not required for successful extinction retention and highlight the complexity of fear inhibition across development.
引用
收藏
页码:158 / 164
页数:7
相关论文
共 46 条
[21]   Immunohistochemical Analyses of Long-Term Extinction of Conditioned Fear in Adolescent Rats [J].
Kim, Jee Hyun ;
Li, Stella ;
Richardson, Rick .
CEREBRAL CORTEX, 2011, 21 (03) :530-538
[22]   Extinction in preweanling rats does not involve NMDA receptors [J].
Kim, Jee Hyun ;
Richardson, Rick .
NEUROBIOLOGY OF LEARNING AND MEMORY, 2010, 94 (02) :176-182
[23]   Fear Extinction across Development: The Involvement of the Medial Prefrontal Cortex as Assessed by Temporary Inactivation and Immunohistochemistry [J].
Kim, Jee Hyun ;
Hamlin, Adam S. ;
Richardson, Rick .
JOURNAL OF NEUROSCIENCE, 2009, 29 (35) :10802-10808
[24]   The effect of the NMDA receptor antagonist MK-801 on the acquisition and extinction of learned fear in the developing rat [J].
Langton, Julia M. ;
Kim, Jee Hyun ;
Nicholas, Jennifer ;
Richardson, Rick .
LEARNING & MEMORY, 2007, 14 (10) :665-668
[25]   The temporal specificity of the switch from NMDAr-dependent extinction to NMDAr-independent re-extinction [J].
Langton, Julia M. ;
Richardson, Rick .
BEHAVIOURAL BRAIN RESEARCH, 2010, 208 (02) :646-649
[26]   UPDATING MEMORIES: CHANGING THE INVOLVEMENT OF THE PRELIMBIC CORTEX IN THE EXPRESSION OF AN INFANT FEAR MEMORY [J].
Li, S. ;
Kim, J. H. ;
Richardson, R. .
NEUROSCIENCE, 2012, 222 :316-325
[27]   Are neuronal nicotinic receptors a target for antiepileptic drug development?: Studies in different seizure models in mice and rats [J].
Löscher, W ;
Potschka, H ;
Wlaz, P ;
Danysz, W ;
Parsons, CG .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2003, 466 (1-2) :99-111
[28]   The endogenous cannabinoid system controls extinction of aversive memories [J].
Marsicano, G ;
Wotjak, CT ;
Azad, SC ;
Bisogno, T ;
Rammes, G ;
Cascio, MG ;
Hermann, H ;
Tang, JR ;
Hofmann, C ;
Zieglgänsberger, W ;
Di Marzo, V ;
Lutz, B .
NATURE, 2002, 418 (6897) :530-534
[29]   Impaired Extinction Retention in Adolescent Rats: Effects of D-Cycloserine [J].
McCallum, Jessica ;
Kim, Jee Hyun ;
Richardson, Rick .
NEUROPSYCHOPHARMACOLOGY, 2010, 35 (10) :2134-2142
[30]   The Endocannabinoid System and the Brain [J].
Mechoulam, Raphael ;
Parker, Linda A. .
ANNUAL REVIEW OF PSYCHOLOGY, VOL 64, 2013, 64 :21-47