PMID- 25712174
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1873-5177 (Electronic)
IS  - 0091-3057 (Linking)
VI  - 132
DP  - 2015 May
TI  - Type 4 phosphodiesterase enzyme inhibitor, rolipram rescues behavioral deficits 
      in olfactory bulbectomy models of depression: Involvement of 
      hypothalamic-pituitary-adrenal axis, cAMP signaling aspects and antioxidant 
      defense system.
PG  - 20-32
LID - S0091-3057(15)00058-1 [pii]
LID - 10.1016/j.pbb.2015.02.017 [doi]
AB  - Olfactory bulbectomy (OBX) model has been proposed as a well documented model of 
      depression. Accumulated evidences suggest that cAMP selective PDE4 enzyme plays 
      an important role in the pathophysiology of depression disorder. Moreover, PDE4 
      inhibitors have shown antidepressant-like effect in behavioral despair models. 
      However, the potential of PDE4 inhibitors to produce antidepressant-like effect 
      in OBX model and their underlying mechanism(s) has not been adequately addressed. 
      The present study was designed to investigate the possible antidepressant-like 
      effects and underlying mechanism of rolipram in OBX model. The effects of 
      rolipram were measured in a battery of behavioral paradigms, including 
      hyperactivity in open field test (OFT), anhedonia behavior in sucrose consumption 
      test, open arm activity in elevated plus maze test (EPM) and emotional scores in 
      hyperemotionality test. The underlying signaling mechanisms were also 
      investigated by measuring serum corticosterone (CORT), brain-derived neurotrophic 
      factor (BDNF) and brain oxidant/antioxidant levels. Treatment with rolipram (0.5 
      and 1mg/kg, p.o., 14days) significantly improved the behavioral anomalies 
      (decreased the hyperactivity, open arm activity and hyperemotionality scores, 
      whereas, increased sucrose consumption). Further, rolipram significantly 
      decreased the CORT level and increased cAMP, pCREB and BDNF levels. Additionally, 
      rolipram reduced oxidative-nitrosative stress markers (lipid peroxidation and 
      nitrite levels) and restored the antioxidant enzyme level, including reduced 
      glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), indicating 
      attenuation of oxidative-nitrosative stress. Our results revealed that 
      antidepressant-like effects of rolipram in OBX model may be mediated by 
      modulating the hypothalamic-pituitary-adrenal (HPA) axis activity, increasing the 
      cAMP signaling aspects and restoring the antioxidant mechanisms.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Jindal, Ankur
AU  - Jindal A
AD  - Department of Pharmacy, Birla Institute of Technology and Science, Pilani, 333031 
      Rajasthan, India. Electronic address: kumarjindal26@gmail.com.
FAU - Mahesh, Radhakrishnan
AU  - Mahesh R
AD  - Department of Pharmacy, Birla Institute of Technology and Science, Pilani, 333031 
      Rajasthan, India.
FAU - Bhatt, Shvetank
AU  - Bhatt S
AD  - Department of Pharmacy, Birla Institute of Technology and Science, Pilani, 333031 
      Rajasthan, India.
LA  - eng
PT  - Journal Article
DEP - 20150221
PL  - United States
TA  - Pharmacol Biochem Behav
JT  - Pharmacology, biochemistry, and behavior
JID - 0367050
OTO - NOTNLM
OT  - Behavioral paradigms
OT  - Depression
OT  - Neurobiological markers
OT  - Olfactory bulbectomy
OT  - Oxidative stress
OT  - Rolipram
EDAT- 2015/02/26 06:00
MHDA- 2015/02/26 06:01
CRDT- 2015/02/26 06:00
PHST- 2014/06/12 00:00 [received]
PHST- 2015/02/15 00:00 [revised]
PHST- 2015/02/17 00:00 [accepted]
PHST- 2015/02/26 06:00 [entrez]
PHST- 2015/02/26 06:00 [pubmed]
PHST- 2015/02/26 06:01 [medline]
AID - S0091-3057(15)00058-1 [pii]
AID - 10.1016/j.pbb.2015.02.017 [doi]
PST - ppublish
SO  - Pharmacol Biochem Behav. 2015 May;132:20-32. doi: 10.1016/j.pbb.2015.02.017. Epub 
      2015 Feb 21.