PMID- 25093543
OWN - NLM
STAT- MEDLINE
DCOM- 20150511
LR  - 20211203
IS  - 1872-7549 (Electronic)
IS  - 0166-4328 (Print)
IS  - 0166-4328 (Linking)
VI  - 273
DP  - 2014 Oct 15
TI  - Asenapine sensitization from adolescence to adulthood and its potential molecular 
      basis.
PG  - 166-76
LID - S0166-4328(14)00491-4 [pii]
LID - 10.1016/j.bbr.2014.07.042 [doi]
AB  - Asenapine is a new antipsychotic drug that induces a long-lasting behavioral 
      sensitization in adult rats. The present study investigated the developmental 
      impacts of adolescent asenapine treatment on drug sensitivity and on 3 proteins 
      implicated in the action of antipsychotic drugs (i.e. brain-derived neurotrophic 
      factor (BDNF), dopamine D2 receptor, and DeltaFosB) in adulthood. Male adolescent 
      Sprague-Dawley rats (postnatal days, P 43-48) were first treated with asenapine 
      (0.05, 0.10 or 0.20mg/kg, sc) and tested in the conditioned avoidance or PCP 
      (2.0mg/kg, sc)-induced hyperlocomotion tasks for 5 days. After they became adults 
      ( approximately P 76), asenapine sensitization was assessed in a single avoidance or 
      PCP-induced hyperlocomotion challenge test with all rats being injected with 
      asenapine (0.10mg/kg, sc). Rats were then sacrificed 1 day later and BDNF, D2 and 
      DeltaFosB in the prefrontal cortex, striatum and hippocampus were examined using 
      Western blotting. In adolescence, repeated asenapine treatment produced a 
      persistent and dose-dependent inhibition of avoidance response, spontaneous motor 
      activity and PCP-induced hyperlocomotion. In the asenapine challenge test, adult 
      rats treated with asenapine (0.10 and 0.20mg/kg) in adolescence made 
      significantly fewer avoidance responses and showed a stronger inhibition of 
      spontaneous motor activity than those previously treated with saline. However, no 
      group difference in the levels of BDNF, D2 and DeltaFosB expression was found. These 
      findings suggest that although adolescent asenapine treatment for a short period 
      of time induces a robust behavioral sensitization that persists into adulthood, 
      such a long-term effect is not likely to be mediated by BDNF, D2 and DeltaFosB.
CI  - Copyright (c) 2014 Elsevier B.V. All rights reserved.
FAU - Shu, Qing
AU  - Shu Q
AD  - Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing 
      Medical University, Nanjing, Jiangsu, PR China; Department of Psychology, 
      University of Nebraska-Lincoln, USA.
FAU - Qin, Rongyin
AU  - Qin R
AD  - Department of Neurology, The Clinical Medical College of Yangzhou University, 
      Yangzhou, Jiangsu, PR China; Department of Psychology, University of 
      Nebraska-Lincoln, USA; Department of Neurology, Changzhou No. 2 People's 
      Hospital, Nanjing Medical University, Changzhou, Jiangsu, PR China.
FAU - Chen, Yingzhu
AU  - Chen Y
AD  - Department of Neurology, The Clinical Medical College of Yangzhou University, 
      Yangzhou, Jiangsu, PR China.
FAU - Hu, Gang
AU  - Hu G
AD  - Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing 
      Medical University, Nanjing, Jiangsu, PR China. Electronic address: 
      ghu@njmu.edu.cn.
FAU - Li, Ming
AU  - Li M
AD  - Department of Psychology, University of Nebraska-Lincoln, USA. Electronic 
      address: mli@unl.edu.
LA  - eng
GR  - R01 MH085635/MH/NIMH NIH HHS/United States
GR  - R01MH085635/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140802
PL  - Netherlands
TA  - Behav Brain Res
JT  - Behavioural brain research
JID - 8004872
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Dibenzocycloheptenes)
RN  - 0 (Fosb protein, rat)
RN  - 0 (Heterocyclic Compounds, 4 or More Rings)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 0 (Receptors, Dopamine D2)
RN  - J1DOI7UV76 (Phencyclidine)
RN  - JKZ19V908O (asenapine)
SB  - IM
MH  - Age Factors
MH  - Animals
MH  - Avoidance Learning/*drug effects
MH  - Brain/*drug effects/*metabolism
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Dibenzocycloheptenes
MH  - Heterocyclic Compounds, 4 or More Rings/administration & dosage/*pharmacology
MH  - Hyperkinesis/chemically induced
MH  - Male
MH  - Motor Activity/*drug effects
MH  - Phencyclidine/toxicity
MH  - Proto-Oncogene Proteins c-fos/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Dopamine D2/metabolism
MH  - Vocalization, Animal/drug effects
PMC - PMC4154364
MID - NIHMS620505
OTO - NOTNLM
OT  - Asenapine
OT  - BDNF
OT  - Conditioned avoidance response
OT  - Dopamine D(2) receptor
OT  - Phencyclidine
OT  - DeltaFosB
COIS- Conflicts of interest: None The authors report no conflicts of interest.
EDAT- 2014/08/06 06:00
MHDA- 2015/05/12 06:00
PMCR- 2015/10/15
CRDT- 2014/08/06 06:00
PHST- 2014/03/31 00:00 [received]
PHST- 2014/07/22 00:00 [revised]
PHST- 2014/07/25 00:00 [accepted]
PHST- 2014/08/06 06:00 [entrez]
PHST- 2014/08/06 06:00 [pubmed]
PHST- 2015/05/12 06:00 [medline]
PHST- 2015/10/15 00:00 [pmc-release]
AID - S0166-4328(14)00491-4 [pii]
AID - 10.1016/j.bbr.2014.07.042 [doi]
PST - ppublish
SO  - Behav Brain Res. 2014 Oct 15;273:166-76. doi: 10.1016/j.bbr.2014.07.042. Epub 
      2014 Aug 2.