PMID- 22361264
OWN - NLM
STAT- MEDLINE
DCOM- 20130517
LR  - 20220309
IS  - 1873-507X (Electronic)
IS  - 0031-9384 (Print)
IS  - 0031-9384 (Linking)
VI  - 107
IP  - 5
DP  - 2012 Dec 5
TI  - The orexin-1 receptor antagonist SB-334867 decreases sympathetic responses to a 
      moderate dose of methamphetamine and stress.
PG  - 743-50
LID - S0031-9384(12)00077-7 [pii]
LID - 10.1016/j.physbeh.2012.02.010 [doi]
AB  - We recently discovered that inhibiting neurons in the dorsomedial hypothalamus 
      (DMH) attenuated hyperthermia, tachycardia, hypertension, and hyperactivity 
      evoked by the substituted amphetamine 3, 4-methylenedioxymethamphetamine (MDMA). 
      Neurons that synthesize orexin are also found in the region of the DMH. As orexin 
      and its receptors are involved in the regulation of heart rate and temperature, 
      they would seem to be logical candidates as mediators of the effects evoked by 
      amphetamines. The goal of this study was to determine if blockade of orexin-1 
      receptors in conscious rats would suppress cardiovascular and thermogenic 
      responses evoked by a range of methamphetamine (METH) doses. Male Sprague-Dawley 
      rats (n=6 per group) were implanted with telemetric transmitters measuring body 
      temperature, heart rate, and mean arterial pressure. Animals were randomized to 
      receive pretreatment with either the orexin-1 receptor antagonist SB-334867 
      (10mg/kg) or an equal volume of vehicle. Thirty minutes later animals were given 
      intraperitoneal (i.p.) injections of either saline, a low (1mg/kg), moderate 
      (5mg/kg) or high (10mg/kg) dose of METH. Pretreatment with SB-334867 
      significantly attenuated increases in body temperature and mean arterial pressure 
      evoked by the moderate but not the low or high dose of METH. Furthermore, animals 
      treated with SB-334867, compared to vehicle, had lower temperature and heart rate 
      increases after the stress of an i.p. injection. In conclusion, temperature and 
      cardiovascular responses to a moderate dose of METH and to stress appear to 
      involve orexin-1 receptors. The failure to affect a low and a high dose of METH 
      suggests a complex pharmacology dependent on dose. A better understanding of this 
      may lead to the knowledge of how monoamines influence the orexin system and vice 
      versa.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Rusyniak, Daniel E
AU  - Rusyniak DE
AD  - Department of Emergency Medicine, Indiana University School of Medicine, 
      Indianapolis, IN 46202, United States. drusynia@iupui.edu
FAU - Zaretsky, Dmitry V
AU  - Zaretsky DV
FAU - Zaretskaia, Maria V
AU  - Zaretskaia MV
FAU - Durant, Pamela J
AU  - Durant PJ
FAU - DiMicco, Joseph A
AU  - DiMicco JA
LA  - eng
GR  - R01 DA026867-02/DA/NIDA NIH HHS/United States
GR  - DA026867/DA/NIDA NIH HHS/United States
GR  - K08 DA020484-05/DA/NIDA NIH HHS/United States
GR  - R01 DA026867/DA/NIDA NIH HHS/United States
GR  - DA020484/DA/NIDA NIH HHS/United States
GR  - K08 DA020484/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120214
PL  - United States
TA  - Physiol Behav
JT  - Physiology & behavior
JID - 0151504
RN  - 0 (1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea)
RN  - 0 (Benzoxazoles)
RN  - 0 (GABA-A Receptor Agonists)
RN  - 0 (Naphthyridines)
RN  - 0 (Orexin Receptors)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Receptors, Neuropeptide)
RN  - 2763-96-4 (Muscimol)
RN  - 44RAL3456C (Methamphetamine)
RN  - 8W8T17847W (Urea)
SB  - IM
MH  - Animals
MH  - Benzoxazoles/*pharmacology
MH  - Blood Pressure/drug effects/physiology
MH  - Body Temperature/drug effects/physiology
MH  - Dose-Response Relationship, Drug
MH  - GABA-A Receptor Agonists/pharmacology
MH  - Male
MH  - Methamphetamine/*antagonists & inhibitors/pharmacology
MH  - Muscimol/pharmacology
MH  - Naphthyridines
MH  - Orexin Receptors
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, G-Protein-Coupled/*antagonists & inhibitors/physiology
MH  - Receptors, Neuropeptide/*antagonists & inhibitors/physiology
MH  - Stress, Psychological/drug therapy/*physiopathology
MH  - Sympathetic Nervous System/drug effects/physiology
MH  - Urea/*analogs & derivatives/pharmacology
PMC - PMC3371311
MID - NIHMS357071
EDAT- 2012/03/01 06:00
MHDA- 2013/05/18 06:00
PMCR- 2013/12/05
CRDT- 2012/02/25 06:00
PHST- 2011/11/29 00:00 [received]
PHST- 2012/02/01 00:00 [revised]
PHST- 2012/02/07 00:00 [accepted]
PHST- 2012/02/25 06:00 [entrez]
PHST- 2012/03/01 06:00 [pubmed]
PHST- 2013/05/18 06:00 [medline]
PHST- 2013/12/05 00:00 [pmc-release]
AID - S0031-9384(12)00077-7 [pii]
AID - 10.1016/j.physbeh.2012.02.010 [doi]
PST - ppublish
SO  - Physiol Behav. 2012 Dec 5;107(5):743-50. doi: 10.1016/j.physbeh.2012.02.010. Epub 
      2012 Feb 14.