PMID- 11249965
OWN - NLM
STAT- MEDLINE
DCOM- 20010510
LR  - 20190726
IS  - 0028-3908 (Print)
IS  - 0028-3908 (Linking)
VI  - 40
IP  - 4
DP  - 2001 Mar
TI  - Administration of myr(+)-G(i2)alpha subunits prevents acute tolerance 
      (tachyphylaxis) to mu-opioid effects in mice.
PG  - 560-9
AB  - The administration of efficacious doses of morphine or beta-endorphin causes 
      acute tolerance (tachyphylaxis) to the effects of additional administrations of 
      these opioids. Mice intracerebroventricularly (icv)-injected with biologically 
      active myristoylated (myr(+))-G(i2)alpha subunits developed no tachyphylaxis to 
      morphine antinociception in the tail-flick test. This treatment increased the 
      potency of opioid-induced analgesia during the declining phase. Moreover, animals 
      showing tachyphylaxis to opioid effects exhibited normal responses to the 
      agonists after icv-administration of myr(+)-G(i2)alpha subunits. In morphine 
      tolerant/dependent mice, an icv dose of 12 pmol/mouse myr(+)-G(i2)alpha subunits 
      facilitated complete restoration of morphine antinociception in only 4 or 5 days 
      instead of the 10 to 11 days required for post-dependent mice. This was observed 
      when myr(+)-G alpha subunits were injected within the first 24 h of chronic 
      morphine administration -- but not later when long-term tolerance takes place. 
      These results suggest that during the course of an opioid effect a progressive 
      reduction of receptor-regulated G-proteins occurs, and hence tachyphylaxis 
      develops. Exogenous administration of myr(+)-G alpha subunits may be of 
      therapeutic potential in improving agonist activity and accelerating the recovery 
      of post-dependent receptors.
FAU - Garzon, J
AU  - Garzon J
AD  - Neurofarmacologia, Instituto de Neurobiologia Santiago Ramon y Cajal, Consejo 
      Superior de Investigaciones Cientificas, Avenida Doctor Arce 37, E-28002 Madrid, 
      Spain. jgarzon@cajal.csic.es
FAU - Sanchez-Blazquez, P
AU  - Sanchez-Blazquez P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Myristates)
RN  - 0 (Receptors, Opioid, mu)
RN  - 36B82AMQ7N (Naloxone)
RN  - 60617-12-1 (beta-Endorphin)
RN  - 76I7G6D29C (Morphine)
RN  - EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gi-Go)
SB  - IM
MH  - Analgesics, Opioid/pharmacology
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Brain/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Drug Tolerance
MH  - GTP-Binding Protein alpha Subunits, Gi-Go/metabolism/*pharmacology
MH  - Injections, Intraventricular
MH  - Male
MH  - Mice
MH  - Morphine/blood/metabolism/pharmacology
MH  - Morphine Dependence/physiopathology
MH  - Myristates/metabolism
MH  - Naloxone/pharmacology
MH  - Nociceptors/drug effects/physiology
MH  - Receptors, Opioid, mu/*physiology
MH  - Substance Withdrawal Syndrome/physiopathology
MH  - Tachyphylaxis/*physiology
MH  - Time Factors
MH  - beta-Endorphin/pharmacology
EDAT- 2001/03/16 10:00
MHDA- 2001/05/22 10:01
CRDT- 2001/03/16 10:00
PHST- 2001/03/16 10:00 [pubmed]
PHST- 2001/05/22 10:01 [medline]
PHST- 2001/03/16 10:00 [entrez]
AID - S0028390800001982 [pii]
AID - 10.1016/s0028-3908(00)00198-2 [doi]
PST - ppublish
SO  - Neuropharmacology. 2001 Mar;40(4):560-9. doi: 10.1016/s0028-3908(00)00198-2.