PMID- 17965976
OWN - NLM
STAT- MEDLINE
DCOM- 20080530
LR  - 20220309
IS  - 0033-3158 (Print)
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Linking)
VI  - 196
IP  - 3
DP  - 2008 Feb
TI  - CRF(1) receptor antagonists attenuate escalated cocaine self-administration in 
      rats.
PG  - 473-82
AB  - RATIONALE: Previous work suggests a role for stress-related 
      corticotropin-releasing factor (CRF) systems in cocaine dependence. However, the 
      involvement of activation of CRF(1) receptors in rats self-administering cocaine 
      with extended access is unknown. OBJECTIVE: The current study examined whether 
      CRF(1) receptor antagonist administration alters cocaine self-administration in 
      animals given extended access. MATERIALS AND METHODS: Wistar rats (n = 32) 
      acquired cocaine self-administration (0.66 mg/kg per infusion) in 1 h sessions 
      for up to 11 days. Rats then were assigned to receive either daily short (1 h, 
      ShA) or long (6 h, LgA) access to cocaine self-administration (n = 7-9 per 
      group). Following escalation of intake, animals received one of two selective 
      CRF(1) antagonists: antalarmin (6.3-25 mg/kg, i.p.) or 
      N,N-bis(2-methoxyethyl)-3-(4-methoxy-2-methylphenyl)-2,5-dimethyl-pyrazolo[1,5a]pyrimidin-7-amine 
      (MPZP; 3.6-27.5 mg/kg, s.c.). RESULTS: By day 11 of the escalation period, LgA 
      rats increased their cocaine intake, reaching an intake level of 15.1 mg/kg, 
      compared to 11.1 mg/kg in ShA rats, during the first hour of sessions. Antalarmin 
      reduced cocaine self-administration at the highest dose selectively in the LgA 
      group but not the ShA group. MPZP reduced cocaine intake both in LgA and ShA 
      rats. However, MPZP did so at a lower dose in LgA rats than in ShA rats. Within 
      the LgA group, MPZP decreased cocaine intake in the first 10 min (loading phase) 
      as well as in the latter session intake (maintenance phase). CONCLUSION: The data 
      suggest that hypersensitivity of the CRF system occurs with extended access to 
      cocaine self-administration and that this altered CRF system may contribute to 
      the increased motivation to self-administer cocaine that develops during 
      psychostimulant dependence.
FAU - Specio, Sheila E
AU  - Specio SE
AD  - The Scripps Research Institute, La Jolla, CA 92037, USA.
FAU - Wee, Sunmee
AU  - Wee S
FAU - O'Dell, Laura E
AU  - O'Dell LE
FAU - Boutrel, Benjamin
AU  - Boutrel B
FAU - Zorrilla, Eric P
AU  - Zorrilla EP
FAU - Koob, George F
AU  - Koob GF
LA  - eng
GR  - R01 DA004398/DA/NIDA NIH HHS/United States
GR  - R01 DA004398-21/DA/NIDA NIH HHS/United States
GR  - DA004398/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20071030
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Dopamine Uptake Inhibitors)
RN  - 0 
      (N,N-bis(2-methoxyethyl)-3-(4-methoxy-2-methylphenyl)-2,5-dimethyl-pyrazolo(1,5-a)pyrimidin-7-amine)
RN  - 0 (Pyrimidines)
RN  - 0 (Pyrroles)
RN  - 0 (Receptors, Corticotropin-Releasing Hormone)
RN  - 0 (antalarmin)
RN  - 5CLY6W2H1M (CRF receptor type 1)
RN  - I5Y540LHVR (Cocaine)
SB  - IM
MH  - Animals
MH  - *Behavior, Addictive
MH  - Cocaine/*administration & dosage
MH  - Dopamine Uptake Inhibitors/*administration & dosage
MH  - Dose-Response Relationship, Drug
MH  - Male
MH  - Pyrimidines/administration & dosage/pharmacology
MH  - Pyrroles/administration & dosage/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Corticotropin-Releasing Hormone/*antagonists & inhibitors
MH  - Self Administration
MH  - Time Factors
PMC - PMC2769571
MID - NIHMS140627
EDAT- 2007/10/30 09:00
MHDA- 2008/05/31 09:00
PMCR- 2009/10/28
CRDT- 2007/10/30 09:00
PHST- 2007/03/12 00:00 [received]
PHST- 2007/10/09 00:00 [accepted]
PHST- 2007/10/30 09:00 [pubmed]
PHST- 2008/05/31 09:00 [medline]
PHST- 2007/10/30 09:00 [entrez]
PHST- 2009/10/28 00:00 [pmc-release]
AID - 10.1007/s00213-007-0983-9 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2008 Feb;196(3):473-82. doi: 
      10.1007/s00213-007-0983-9. Epub 2007 Oct 30.