PMID- 30995444
OWN - NLM
STAT- MEDLINE
DCOM- 20200130
LR  - 20200130
IS  - 1095-6867 (Electronic)
IS  - 0018-506X (Linking)
VI  - 113
DP  - 2019 Jul
TI  - Sex-specific differences in adult cognition and neuroplasticity following 
      repeated combinatory stress and TrkB receptor antagonism in adolescence.
PG  - 21-37
LID - S0018-506X(18)30431-8 [pii]
LID - 10.1016/j.yhbeh.2019.04.006 [doi]
AB  - Evidence supports brain-derived neurotrophic factor (BDNF) and its primary 
      receptor tyrosine-related kinase B (TrkB) as targets in the treatment of mood 
      disorders. This study characterized the impact of a 10-day combinatory stress 
      paradigm (alternating days of restraint stress and forced swim) and 
      administration of the selective TrkB antagonist ANA-12 (0.5 mg/kg, i.p.) during 
      adolescence in male and female Wistar rats on adulthood behavioral and 
      neurochemical responses. The social interaction/preference (SIT/SP), and Y maze 
      conditioned place preference (YMCPP) and passive avoidance tests (YMPAT), 
      initiated on PND 62, served to determine sex-related behavioral responses. 
      Results support reduced sociability in females in the SIT/SP, but no impact of 
      ANA-12 to regulate sociability or social memory. Blockade of TrkB during 
      adolescence facilitated YMCPP-related reward behavior in both sexes, and reduced 
      YMPAT fear conditioning in females. Following behavioral testing, rats were 
      exposed to 5-min acute forced swim and brains collected 2 h post swim to 
      determine effects of adolescent TrkB blockade and stress exposure on 
      neurochemical regulators of stress and plasticity. Findings show elevated 
      glucocorticoid receptor (GR-) and TrkB-immunoreactivity (ir) in the amygdalar 
      central nucleus, and GR-ir in the hypothalamic paraventricular nucleus of females 
      compared to males. In the hippocampal CA1, BDNF-ir was lower in females versus 
      males, and GR-ir was elevated in stress versus non-stress males. Together, we 
      demonstrate that inherent sex-specific differences, which may modulate impact of 
      adolescence stress exposure and TrkB inhibition, differentially affect male and 
      female adulthood behavior and biochemical response profiles, suggesting that 
      these responses are in part conditioned by prior experience.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Azogu, Idu
AU  - Azogu I
AD  - Behavioral Neuroscience Group, School of Psychology, University of Ottawa, 136 
      Jean-Jacques Lussier, Ottawa, ON, Canada.
FAU - Cossette, Isabelle
AU  - Cossette I
AD  - Behavioral Neuroscience Group, School of Psychology, University of Ottawa, 136 
      Jean-Jacques Lussier, Ottawa, ON, Canada.
FAU - Mukunzi, Joana
AU  - Mukunzi J
AD  - Behavioral Neuroscience Group, School of Psychology, University of Ottawa, 136 
      Jean-Jacques Lussier, Ottawa, ON, Canada.
FAU - Ibeke, Ogechi
AU  - Ibeke O
AD  - Behavioral Neuroscience Group, School of Psychology, University of Ottawa, 136 
      Jean-Jacques Lussier, Ottawa, ON, Canada.
FAU - Plamondon, Helene
AU  - Plamondon H
AD  - Behavioral Neuroscience Group, School of Psychology, University of Ottawa, 136 
      Jean-Jacques Lussier, Ottawa, ON, Canada. Electronic address: 
      hplamond@uottawa.ca.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190508
PL  - United States
TA  - Horm Behav
JT  - Hormones and behavior
JID - 0217764
RN  - 0 (ANA 12 compound)
RN  - 0 (Azepines)
RN  - 0 (Benzamides)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Glucocorticoids)
RN  - 0 (Receptors, Glucocorticoid)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Azepines/*pharmacology
MH  - Benzamides/*pharmacology
MH  - Brain/drug effects/metabolism
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cognition/*drug effects
MH  - Fear/drug effects
MH  - Female
MH  - Glucocorticoids/pharmacology
MH  - Hippocampus/drug effects/metabolism
MH  - Male
MH  - Memory/drug effects
MH  - Neuronal Plasticity/*drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, trkB/*antagonists & inhibitors/metabolism
MH  - Receptors, Glucocorticoid/metabolism
MH  - Sex Characteristics
MH  - Sexual Maturation/*drug effects/physiology
MH  - *Stress, Psychological/physiopathology/psychology
OTO - NOTNLM
OT  - ANA-12
OT  - BDNF
OT  - Combinatory stress
OT  - GR
OT  - Sex-specific differences
OT  - TrkB
EDAT- 2019/04/18 06:00
MHDA- 2020/01/31 06:00
CRDT- 2019/04/18 06:00
PHST- 2018/10/03 00:00 [received]
PHST- 2019/04/09 00:00 [revised]
PHST- 2019/04/09 00:00 [accepted]
PHST- 2019/04/18 06:00 [pubmed]
PHST- 2020/01/31 06:00 [medline]
PHST- 2019/04/18 06:00 [entrez]
AID - S0018-506X(18)30431-8 [pii]
AID - 10.1016/j.yhbeh.2019.04.006 [doi]
PST - ppublish
SO  - Horm Behav. 2019 Jul;113:21-37. doi: 10.1016/j.yhbeh.2019.04.006. Epub 2019 May 
      8.