PMID- 1608292
OWN - NLM
STAT- MEDLINE
DCOM- 19920717
LR  - 20190701
IS  - 0024-3205 (Print)
IS  - 0024-3205 (Linking)
VI  - 50
IP  - 26
DP  - 1992
TI  - alpha N-acetyl human beta-endorphin-(1-31) alleviates the morphine withdrawal 
      syndrome in rodents: a comparative study with clonidine.
PG  - 2099-109
AB  - The potential effect of intracerebroventricular (icv) alpha N-acetyl human 
      beta-endorphin-(1-31) on morphine dependence was examined in mice and rats. 
      Animals were rendered tolerant-dependent by subcutaneous (sc) implantation of an 
      oily suspension (10 ml/Kg mouse and 3 ml/Kg rat) containing 0.1 g/ml of morphine. 
      After 72 h of chronic morphine, 1 mg/Kg sc naloxone precipitated in both species 
      a withdrawal syndrome that was moderate in animals pretreated with the acetylated 
      derivative of beta-endorphin. Doses of 28 fmols/rat or 80 fmols/mouse alpha 
      N-acetyl human beta-endorphin-(1-31) reduced the number of animals presenting the 
      jumping behaviour, as well as the number of jumps recorded. Moreover, less than 
      half of the rats presented the other withdrawal signs evaluated: squeak on touch, 
      diarrhoea, chattering, chewing, ptosis and body shakes. This activity could be 
      observed when alpha N-acetyl human beta-endorphin was injected 1 h to 24 h before 
      naloxone; longer intervals resulted in a significant loss of this activity. The 
      alpha 2 agonist clonidine given icv at pmol-nmol doses decreased the incidence of 
      morphine withdrawal syndrome. Combinations of these two substances generally did 
      not produce any further enhancement of the effects of clonidine and alpha 
      N-acetyl beta-endorphin when used alone. Icv injections of the antagonist of 
      alpha 2-adrenoceptors yohimbine prevented both clonidine and alpha N-acetyl 
      beta-endorphin-(1-31) from reducing the jumping behaviour displayed by 
      morphine-abstinent mice. It is suggested that alpha N-acetyl beta-endorphin 
      produces this alleviation of the morphine withdrawal syndrome by improving the 
      efficiency of alpha 2-mediated agonist effects after acting on a neural substrate 
      that is distinct from the mu opioid receptor binding site.
FAU - Garzon, J
AU  - Garzon J
AD  - Neuropharmacology Unit, Cajal Institute, Madrid, Spain.
FAU - Sanchez-Blazquez, P
AU  - Sanchez-Blazquez P
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 2Y49VWD90Q (Yohimbine)
RN  - 36B82AMQ7N (Naloxone)
RN  - 60617-12-1 (beta-Endorphin)
RN  - 75719-50-5 (N-acetyl-beta-endorphin)
RN  - 76I7G6D29C (Morphine)
RN  - MN3L5RMN02 (Clonidine)
SB  - IM
MH  - Animals
MH  - Clonidine/antagonists & inhibitors/*therapeutic use
MH  - Disease Models, Animal
MH  - Male
MH  - Mice
MH  - Morphine/*adverse effects
MH  - Naloxone/therapeutic use
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Substance Withdrawal Syndrome/*prevention & control
MH  - Yohimbine/pharmacology
MH  - beta-Endorphin/*analogs & derivatives/antagonists & inhibitors/therapeutic use
EDAT- 1992/01/01 00:00
MHDA- 1992/01/01 00:01
CRDT- 1992/01/01 00:00
PHST- 1992/01/01 00:00 [pubmed]
PHST- 1992/01/01 00:01 [medline]
PHST- 1992/01/01 00:00 [entrez]
AID - 0024-3205(92)90576-B [pii]
AID - 10.1016/0024-3205(92)90576-b [doi]
PST - ppublish
SO  - Life Sci. 1992;50(26):2099-109. doi: 10.1016/0024-3205(92)90576-b.