PMID- 7891326
OWN - NLM
STAT- MEDLINE
DCOM- 19950414
LR  - 20141120
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 272
IP  - 3
DP  - 1995 Mar
TI  - Alkylation of mu opioid receptors by beta-funaltrexamine in vivo: comparison of 
      the effects on in situ binding and heroin self-administration in rats.
PG  - 1135-40
AB  - Mu opioid receptors are known to be directly involved in the reinforcing effects 
      of opiates; however, little is known regarding the relationship between 
      alteration of mu opioid receptor binding and opiate reinforcement. 
      Intracerebroventricular (i.c.v.) administration of beta-funaltrexamine (beta-FNA) 
      has been shown to reduce the number of mu opioid receptors throughout the brain 
      and can be used to address questions regarding the relationship of the density of 
      these receptors to the pharmacological effects of opiates. The time course of the 
      effects of beta-FNA on heroin self-administration was compared with the effects 
      on mu opioid receptor binding. beta-FNA (40 nmol) or saline was administered 
      i.c.v. to animals trained to self-administer either 18 or 60 micrograms/kg per 
      infusion of heroin. The number of infusions decreased after beta-FNA 
      administration but steadily returned to base-line levels approximately 10 days 
      after beta-FNA treatment. The time course of the effects of beta-FNA on mu opioid 
      receptor binding was determined in separate groups of animals. beta-FNA treatment 
      decreased the number of [3H]D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin binding sites by 
      34 to 50% in rat brain sections; an effect that persisted for up to 18 days. The 
      affinity was unaffected initially, but decreased in a linear manner from days 9 
      to 18 after beta-FNA administration. The return of heroin self-administration 
      before the return of mu opioid receptor binding suggests that the recovery of mu 
      opioid receptor function after beta-FNA treatment is more complex than merely 
      synthesis of new receptors.
FAU - Martin, T J
AU  - Martin TJ
AD  - Department of Physiology and Pharmacology, Bowman Gray School of Medicine/Wake 
      Forest University, Winston-Salem, North Carolina.
FAU - Dworkin, S I
AU  - Dworkin SI
FAU - Smith, J E
AU  - Smith JE
LA  - eng
GR  - DA-00114/DA/NIDA NIH HHS/United States
GR  - DA-01999/DA/NIDA NIH HHS/United States
GR  - DA-06634/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Enkephalins)
RN  - 0 (Receptors, Opioid, mu)
RN  - 100929-53-1 (Enkephalin, Ala(2)-MePhe(4)-Gly(5)-)
RN  - 5S6W795CQM (Naltrexone)
RN  - 70D95007SX (Heroin)
RN  - 72782-05-9 (beta-funaltrexamine)
SB  - IM
MH  - Alkylation
MH  - Animals
MH  - Behavior, Animal
MH  - Binding, Competitive
MH  - Brain/metabolism
MH  - Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
MH  - Enkephalins/metabolism
MH  - Heroin/*metabolism
MH  - In Vitro Techniques
MH  - Injections, Intraventricular
MH  - Naltrexone/administration & dosage/*analogs & derivatives/metabolism
MH  - Rats
MH  - Rats, Inbred F344
MH  - Receptors, Opioid, mu/*chemistry
MH  - Self Administration
EDAT- 1995/03/01 00:00
MHDA- 1995/03/01 00:01
CRDT- 1995/03/01 00:00
PHST- 1995/03/01 00:00 [pubmed]
PHST- 1995/03/01 00:01 [medline]
PHST- 1995/03/01 00:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 1995 Mar;272(3):1135-40.