Effect of social isolation on the metabolism of morphine and its passage through the blood-brain barrier and on consumption of sucrose solutions.
BACKGROUND
We have previously shown that place preference conditioning to morphine was observed in social mice at the dose of 8 mg/kg, whereas 4 weeks of isolation impairs the place preference conditioning to morphine (8-100 mg/kg).


OBJECTIVE
The present study, aimed at explaining this phenomenon, tested three hypotheses: firstly, a reduced sensitivity to reinforcers induced by isolation; secondly, a difference in morphine disposition in isolated and social mice; thirdly, an altered blood-brain barrier transport of morphine in isolated mice.


METHODS
In the sucrose experiments, mice had the choice (for 24 h) between a bottle containing tap water and a bottle containing a sucrose solution. Three sucrose concentrations were used: 0.5, 1 and 2% (weight/weight). In the morphine disposition experiments, the plasma levels of morphine and of morphine-3-glucuronide (M3G) were measured for 240 min. The brain concentrations of morphine was measured at 15 and 30 min. The passage of morphine through the blood-brain barrier was measured using a method modified from that of Takasato (1984).


RESULTS
The preference for the sucrose solutions was significantly greater in isolated than in social mice for the concentration of 2%. Isolation reduced the plasma levels of morphine and of M3G, but did not alter the brain concentration of morphine. The passage of morphine through the blood-brain barrier was altered by isolation in neither of the eight structures examined.


CONCLUSIONS
We conclude that the behavioural effect of isolation observed in the conditioned place preference to morphine may depend on changes both in morphine disposition and in the sensitivity to reinforcers in isolated mice.
Coudereau
J P
JP
INSERM U. 26, Hôpital Fernand Widal, Paris, France.
Stain
F
F
Drion
N
N
Sandouk
P
P
Monier
C
C
Debray
M
M
Scherrmann
J M
JM
Bourre
J M
JM
Francès
H
H
D000701:Analgesics, Opioid / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004435:Eating / Q000187:drug effects; D008297:Male; D051379:Mice; D009020:Morphine / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D009022:Morphine Derivatives / Q000097:blood; D012934:Social Isolation; D013395:Sucrose / Q000378:metabolism*
D000701:Analgesics, Opioid; D009022:Morphine Derivatives; D013395:Sucrose; D009020:Morphine; C018108:morphine-3-glucuronide