Alterations in Blood-Brain Barrier Function by Morphine and Methamphetamine

:  The possibility that stress associated with morphine and amphetamine administration or withdrawal will influence the blood–brain barrier (BBB) and brain dysfunction was examined in a rodent model. Repeated daily administration of morphine (10 mg/kg, i.p.) resulted in drug dependence in rats on th...

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Bibliographic Details
Published in:Annals of the New York Academy of Sciences 2006-08, Vol.1074 (1), p.198-224
Main Authors: SHARMA, HARI SHANKER, ALI, SYED F.
Format: Article
Language:English
Subjects:
Analgesia - methods
Animals
blood-brain barrier
Blood-Brain Barrier - drug effects
Blood-Brain Barrier - physiology
brain dysfunction
Evans blue
Fever
glial cells
heat shock protein
HSP72 Heat-Shock Proteins - metabolism
methamphetamine
Methamphetamine - pharmacokinetics
Mice
morphine
Morphine - pharmacokinetics
Morphine Dependence
nerve cells
Neuroglia - physiology
Neurons - physiology
Neuropil - ultrastructure
radioiodine
Rats
Rats, Sprague-Dawley
stress
Substance Withdrawal Syndrome
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Summary::  The possibility that stress associated with morphine and amphetamine administration or withdrawal will influence the blood–brain barrier (BBB) and brain dysfunction was examined in a rodent model. Repeated daily administration of morphine (10 mg/kg, i.p.) resulted in drug dependence in rats on the sixth day and onwards. Measurement of the BBB permeability to large molecule tracers normally bound to proteins, e.g., Evans blue albumin and radioiodine ([131]Iodine) did not show any leakage on the 12th day of drug dependence. On the other hand, spontaneous withdrawal of morphine on day 1 resulted in profound stress symptoms. These symptoms were much more intense on the second day of morphine withdrawal. Alterations in the BBB to protein tracers were seen in several regions of the brain. This increase in BBB to protein tracers was most pronounced on the second day of morphine withdrawal. These rats also exhibited abnormal neuronal, glial and stress protein, the heat‐shock protein 72 kD (HSP‐72 kD) response. On the other hand, acute administration of methamphetamine (40 mg/kg, i.p.) in mice resulted in marked extravasation of endogenous serum protein as seen with increased expression of albumin immunohistochemistry. These observations suggest that psychostimulants and associated stress are capable to influence the brain function, probably through modifying the BBB function, not reported earlier.
ISSN:0077-8923
1749-6632
DOI:10.1196/annals.1369.020