PMID- 21167239
OWN - NLM
STAT- MEDLINE
DCOM- 20110505
LR  - 20141120
IS  - 1873-5169 (Electronic)
IS  - 0196-9781 (Linking)
VI  - 32
IP  - 2
DP  - 2011 Feb
TI  - Evidence for the participation of cocaine- and amphetamine-regulated transcript 
      peptide (CART) in the fluoxetine-induced anti-hyperalgesia in neuropathic rats.
PG  - 317-26
LID - 10.1016/j.peptides.2010.09.030 [doi]
AB  - Cocaine- and amphetamine-regulated transcript peptide (CART) has a role in 
      chronic pain, and also in the actions of selective serotonin reuptake inhibitors 
      (SSRIs) employed in the treatment of neuropathic pain. Herein, we test the 
      hypothesis that CART may mediate the anti-hyperalgesic effect of the SSRI, 
      fluoxetine, in neuropathic rats. Sciatic nerve in the right hind paw of rat was 
      ligated to induce neuropathic pain, and the paw withdrawal latency was evaluated 
      using Hargreaves apparatus. Fluoxetine [5-25mg/kg, intraperitoneal (ip)] or CART 
      (54-102) [0.1-1.5mug/rat, intracerebroventricular (icv)] dose-dependently 
      attenuated the hyperalgesic response observed in neuropathic rats, indicating 
      anti-nociceptive properties of each agent. The anti-hyperalgesic effect of 
      fluoxetine was potentiated by the subeffective dose of CART, and attenuated by 
      CART-antibody (1:500 dilution; 5mul/rat, icv); CART-antibody had no effect per se. 
      Isobolographic analysis showed a significant synergism between fluoxetine and 
      CART, and antagonism between fluoxetine and CART-antibody. Immunocytochemical 
      labeling with monoclonal antibodies against CART showed drastic increase in 
      CART-immunoreactive fibers in the ventrolateral periaqueductal gray (VLPAG; 
      116%), dorsal subdivision of dorsal raphe nucleus (DRD; 176%), and locus 
      coeruleus (LC; 733%) of neuropathic animals. Fluoxetine treatment significantly 
      reduced the immunoreactivity in these areas. However, CART-immunoreactive cells 
      and fibers in the arcuate nucleus did not respond to neuropathy or fluoxetine 
      treatments. We suggest that the CART innervation of DRD, LC and VLPAG may be 
      involved in the (i) central processing of neuropathic pain and (ii) 
      fluoxetine-induced anti-hyperalgesic effect in neuropathic pain.
CI  - Copyright A(c) 2010 Elsevier Inc. All rights reserved.
FAU - Upadhya, Manoj A
AU  - Upadhya MA
AD  - Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur 
      University Campus, Nagpur 440033, India.
FAU - Dandekar, Manoj P
AU  - Dandekar MP
FAU - Kokare, Dadasaheb M
AU  - Kokare DM
FAU - Singru, Praful S
AU  - Singru PS
FAU - Subhedar, Nishikant K
AU  - Subhedar NK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101215
PL  - United States
TA  - Peptides
JT  - Peptides
JID - 8008690
RN  - 0 (Antibodies)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (cocaine- and amphetamine-regulated transcript protein)
RN  - 01K63SUP8D (Fluoxetine)
SB  - IM
MH  - Animals
MH  - Antibodies/immunology/pharmacology
MH  - Arcuate Nucleus of Hypothalamus/drug effects/metabolism
MH  - Brain/drug effects/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions/physiology
MH  - Fluoxetine/administration & dosage/pharmacology/*therapeutic use
MH  - Hyperalgesia/*drug therapy/metabolism
MH  - Infusions, Intraventricular
MH  - Ligation
MH  - Locus Coeruleus/drug effects/metabolism
MH  - Male
MH  - Nerve Fibers/drug effects/metabolism
MH  - Nerve Tissue Proteins/administration & 
      dosage/immunology/*metabolism/pharmacology/therapeutic use
MH  - Pain Measurement
MH  - Periaqueductal Gray/drug effects/metabolism
MH  - Raphe Nuclei/drug effects/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sciatic Nerve/surgery
EDAT- 2010/12/21 06:00
MHDA- 2011/05/06 06:00
CRDT- 2010/12/21 06:00
PHST- 2010/08/07 00:00 [received]
PHST- 2010/09/24 00:00 [revised]
PHST- 2010/09/25 00:00 [accepted]
PHST- 2010/12/21 06:00 [entrez]
PHST- 2010/12/21 06:00 [pubmed]
PHST- 2011/05/06 06:00 [medline]
AID - S0196-9781(10)00528-0 [pii]
AID - 10.1016/j.peptides.2010.09.030 [doi]
PST - ppublish
SO  - Peptides. 2011 Feb;32(2):317-26. doi: 10.1016/j.peptides.2010.09.030. Epub 2010 
      Dec 15.