PMID- 22516018
OWN - NLM
STAT- MEDLINE
DCOM- 20130401
LR  - 20131121
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 212
DP  - 2012 Jun 14
TI  - Sleep homeostasis and depression: studies with the rat clomipramine model of 
      depression.
PG  - 149-58
LID - 10.1016/j.neuroscience.2012.03.029 [doi]
AB  - Neonatal treatment of rat pups with clomipramine (CLI) has been shown to cause 
      long-lasting and persistent depression-related behaviors and changes in sleep 
      architecture and in brain-derived neurotrophic factor (BDNF) signaling in adult 
      animals, producing an animal model of depression. However, the molecular 
      mechanisms which mediate these effects of early-life CLI treatment on adult 
      animals remain largely unknown. In order to characterize these further, we 
      investigated in neonatally CLI-treated rats the sleep architecture as well as the 
      extracellular and cellular levels of sleep regulators (nitric oxide, adenosine) 
      and BDNF, respectively, in the basal forebrain (BF), i.e. the brain area which is 
      implicated in sleep and depression. We found that CLI-treated rats exhibited a 
      disturbed sleep architecture (REM sleep fragmentation was increased and NREM 
      periods preceding REM were shorter) and reduced levels of BDNF and adenosine in 
      the BF, whereas the levels of nitric oxide were elevated. Next, we examined sleep 
      deprivation (SD)-induced homeostatic responses on sleep regulation and brain BDNF 
      levels in CLI-treated rats. Compared to control rats, 3h of SD induced a smaller 
      increase in the amount of NREM sleep during sleep recovery. At the molecular 
      level, the normal homeostatic response was dissociated: the rise in the adenosine 
      level was not accompanied by a rise in the nitric oxide concentration. Moreover, 
      while BF BDNF levels decreased during SD in control rats, such a decline was not 
      observed in CLI rats. Taken together, neonatal CLI treatment produces 
      long-lasting functional changes in the sleep architecture and sleep regulation in 
      adult rats, accompanied by dysregulated BDNF signaling in the BF.
CI  - Copyright (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Savelyev, S A
AU  - Savelyev SA
AD  - Institute of Biomedicine, Department of Physiology, University of Helsinki, P.O. 
      Box 63 (Haartmaninkatu 8), 00014 Helsinki, Finland. sergey.saveljev@gmail.com
FAU - Rantamaki, T
AU  - Rantamaki T
FAU - Rytkonen, K-M
AU  - Rytkonen KM
FAU - Castren, E
AU  - Castren E
FAU - Porkka-Heiskanen, T
AU  - Porkka-Heiskanen T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120416
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Antidepressive Agents, Tricyclic)
RN  - NUV44L116D (Clomipramine)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Antidepressive Agents, Tricyclic/*pharmacology
MH  - Behavior, Animal/drug effects/physiology
MH  - Clomipramine/*pharmacology
MH  - Depressive Disorder/*chemically induced/drug therapy/physiopathology
MH  - Disease Models, Animal
MH  - Homeostasis/*drug effects/physiology
MH  - Male
MH  - Prosencephalon/*drug effects/growth & development/physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Sleep, REM/*drug effects/physiology
EDAT- 2012/04/21 06:00
MHDA- 2013/04/02 06:00
CRDT- 2012/04/21 06:00
PHST- 2011/10/28 00:00 [received]
PHST- 2012/03/22 00:00 [revised]
PHST- 2012/03/23 00:00 [accepted]
PHST- 2012/04/21 06:00 [entrez]
PHST- 2012/04/21 06:00 [pubmed]
PHST- 2013/04/02 06:00 [medline]
AID - S0306-4522(12)00290-4 [pii]
AID - 10.1016/j.neuroscience.2012.03.029 [doi]
PST - ppublish
SO  - Neuroscience. 2012 Jun 14;212:149-58. doi: 10.1016/j.neuroscience.2012.03.029. 
      Epub 2012 Apr 16.