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A Potent Serotonin‐Modulating Compound AP‐267 Attenuates Morphine Withdrawal‐Induced Blood–Brain Barrier Dysfunction in Rats
Author(s) -
SHARMA HARI S.,
LUNDSTEDT TORBJÖRN,
BOMAN ARNE,
LEK PER,
SEIFERT ELISABETH,
WIKLUND LARS,
ALI SYED F.
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1369.049
Subject(s) - serotonin , 5 ht2c receptor , evans blue , morphine , blood–brain barrier , 5 ht receptor , receptor , endocrinology , medicine , pharmacology , analgesic , chemistry , anesthesia , central nervous system
The possibility that a serotonin 5‐HT2c receptor‐modulating compound, AP‐267, will influence spontaneous morphine withdrawal symptoms and the alterations in the brain fluid microenvironment was examined in a rat model. Daily administration of morphine (10 mg/kg, i.p.) for 10 days resulted in dependence of rats as seen by loss of analgesic response. On the 11th day, no morphine administration was given. This resulted in profound withdrawal symptoms 24 h after morphine withdrawal. The magnitude and severity of these symptoms were increased further 48 h after withdrawal. Measurement of the blood‐brain barrier (BBB) permeability, a measure of perturbed brain fluid microenvironment showed leakage of Evans blue and radioiodine tracers in several parts of the brain in rats showing withdrawal symptoms. Whereas, rats treated with AP‐267 either on the 1st day or 2nd day morphine withdrawal showed much less symptoms and leakage of the BBB. Taken together, these observations suggest that ( a ) stress associated with the withdrawal symptoms are sufficient enough to induce breakdown of the BBB function, and ( b ) modulation of serotonin 5‐HT2c receptors may have some protective influence on the stress symptoms and the BBB disruption.