PMID- 23590881
OWN - NLM
STAT- MEDLINE
DCOM- 20140314
LR  - 20211021
IS  - 1469-5111 (Electronic)
IS  - 1461-1457 (Print)
IS  - 1461-1457 (Linking)
VI  - 16
IP  - 8
DP  - 2013 Sep
TI  - Corticotropin-releasing factor (CRF) and alpha 2 adrenergic receptors mediate heroin 
      withdrawal-potentiated startle in rats.
PG  - 1867-75
LID - 10.1017/S1461145713000308 [doi]
AB  - Anxiety is one of the early symptoms of opioid withdrawal and contributes to 
      continued drug use and relapse. The acoustic startle response (ASR) is a 
      component of anxiety that has been shown to increase during opioid withdrawal in 
      both humans and animals. We investigated the role of corticotropin-releasing 
      factor (CRF) and norepinephrine (NE), two key mediators of the brain stress 
      system, on acute heroin withdrawal-potentiated ASR. Rats injected with heroin 
      (2 mg/kg s.c.) displayed an increased ASR when tested 4 h after heroin treatment. 
      A similar increase in ASR was found in rats 10-20 h into withdrawal from extended 
      access (12 h) to i.v. heroin self-administration, a model that captures several 
      aspects of heroin addiction in humans. Both the alpha 2 adrenergic receptor agonist 
      clonidine (10 mug/kg s.c.) and CRF1 receptor antagonist 
      N,N-bis(2-methoxyethyl)-3-(4-methoxy-2-methylphenyl)-2,5-dimethyl-pyrazolo[1,5-a] 
      pyrimidin-7-amine (MPZP; 20 mg/kg s.c.) blocked heroin withdrawal-potentiated 
      startle. To investigate the relationship between CRF1 and alpha 2 adrenergic 
      receptors in the potentiation of the ASR, we tested the effect of MPZP on 
      yohimbine (1.25 mg/kg s.c.)-potentiated startle and clonidine on CRF (2 mug 
      i.c.v.)-potentiated startle. Clonidine blocked CRF-potentiated startle, whereas 
      MPZP partially attenuated but did not reverse yohimbine-potentiated startle, 
      suggesting that CRF may drive NE release to potentiate startle. These results 
      suggest that CRF1 and alpha 2 receptors play an important role in the heightened 
      anxiety-like behaviour observed during acute withdrawal from heroin, possibly via 
      CRF inducing the release of NE in stress-related brain regions.
FAU - Park, Paula E
AU  - Park PE
AD  - Committee on the Neurobiology of Addictive Disorders, The Scripps Research 
      Institute, La Jolla, CA 92037, USA.
FAU - Vendruscolo, Leandro F
AU  - Vendruscolo LF
FAU - Schlosburg, Joel E
AU  - Schlosburg JE
FAU - Edwards, Scott
AU  - Edwards S
FAU - Schulteis, Gery
AU  - Schulteis G
FAU - Koob, George F
AU  - Koob GF
LA  - eng
GR  - T32DA73157/DA/NIDA NIH HHS/United States
GR  - DA004043/DA/NIDA NIH HHS/United States
GR  - R37 AA008459/AA/NIAAA NIH HHS/United States
GR  - T32 DA007315/DA/NIDA NIH HHS/United States
GR  - R01 AA008459/AA/NIAAA NIH HHS/United States
GR  - AA008459/AA/NIAAA NIH HHS/United States
GR  - R01 DA004043/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20130416
PL  - England
TA  - Int J Neuropsychopharmacol
JT  - The international journal of neuropsychopharmacology
JID - 9815893
RN  - 0 (Adrenergic alpha-2 Receptor Agonists)
RN  - 0 (Adrenergic alpha-2 Receptor Antagonists)
RN  - 0 
      (N,N-bis(2-methoxyethyl)-3-(4-methoxy-2-methylphenyl)-2,5-dimethyl-pyrazolo(1,5-a)pyrimidin-7-amine)
RN  - 0 (Narcotics)
RN  - 0 (Pyrimidines)
RN  - 0 (Receptors, Adrenergic, alpha-2)
RN  - 2Y49VWD90Q (Yohimbine)
RN  - 70D95007SX (Heroin)
RN  - 9015-71-8 (Corticotropin-Releasing Hormone)
RN  - MN3L5RMN02 (Clonidine)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Acoustic Stimulation
MH  - Adrenergic alpha-2 Receptor Agonists/pharmacology
MH  - Adrenergic alpha-2 Receptor Antagonists/pharmacology
MH  - Analysis of Variance
MH  - Animals
MH  - Clonidine/pharmacology
MH  - Conditioning, Operant/drug effects
MH  - Corticotropin-Releasing Hormone/antagonists & inhibitors/*metabolism/pharmacology
MH  - Disease Models, Animal
MH  - Heroin/*adverse effects
MH  - Male
MH  - Narcotics/*adverse effects
MH  - Norepinephrine/metabolism
MH  - Psychoacoustics
MH  - Pyrimidines/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Adrenergic, alpha-2/*metabolism
MH  - Reflex, Startle/drug effects/*physiology
MH  - Self Administration
MH  - Substance Withdrawal Syndrome/drug therapy/metabolism/*physiopathology
MH  - Time Factors
MH  - Yohimbine/pharmacology
PMC - PMC3880138
MID - NIHMS539869
COIS- Statement of Interest None.
EDAT- 2013/04/18 06:00
MHDA- 2014/03/15 06:00
PMCR- 2014/09/01
CRDT- 2013/04/18 06:00
PHST- 2013/04/18 06:00 [entrez]
PHST- 2013/04/18 06:00 [pubmed]
PHST- 2014/03/15 06:00 [medline]
PHST- 2014/09/01 00:00 [pmc-release]
AID - S1461145713000308 [pii]
AID - 10.1017/S1461145713000308 [doi]
PST - ppublish
SO  - Int J Neuropsychopharmacol. 2013 Sep;16(8):1867-75. doi: 
      10.1017/S1461145713000308. Epub 2013 Apr 16.