Changes in blood-brain barrier permeability to drugs in decompressed rats.
A study has been made of changes in permeability of the blood-brain barrier (BBB) to drugs following exposure to compression-decompression. Fifty-five rats were exposed to 6.1 b (abs) air for 90 min and subsequently linearly decompressed to the ambient pressure during a period of 3 min. Thirty-five rats serving as controls were kept at the ambient pressure. Catalepsy, which is mediated through the striatal dopamine receptors, was used as a behavioral indicator for the penetration of drugs into the brain. A comparison was made between drugs that normally pass the BBB (atropine, 10 mg/kg; haloperidol, 2 mg/kg) and drugs that do not readily pass the BBB as a rule (methylatropine, 10 mg/kg; domperidone, 10-20 mg/kg). Evans blue, injected intravenously, was used for the visualization of possible changes in the BBB permeability. It was found that methylatropine significantly prevented haloperidol-induced catalepsy in decompressed rats, in comparison with control rats. However, this prevention was not so intense as that found after injection of a similar dose of atropine. Domperidone induced a weak catalepsy in decompressed rats, but failed to induce any catalepsy in control rats. Gross and fluorescence-microscopic examination revealed an increased penetration of Evans blue into the brains of the decompressed rats. It is concluded that compression-decompression exposure can induce a limited but significant breakage of the BBB, leading to an increase in the central effects of the drugs that normally display poor penetration of the BBB. The measurement of behavioral changes provided a new and relevant technique for studying the changes of BBB permeability to drugs.
D000818:Animals; D001285:Atropine / Q000378:metabolism; D001286:Atropine Derivatives / Q000378:metabolism / Q000633:toxicity; D001812:Blood-Brain Barrier; D002375:Catalepsy / Q000139:chemically induced; D003665:Decompression Sickness / Q000378:metabolism*; D004294:Domperidone / Q000378:metabolism / Q000633:toxicity; D006220:Haloperidol / Q000378:metabolism; D006801:Humans; D008297:Male; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D001286:Atropine Derivatives; D004364:Pharmaceutical Preparations; D004294:Domperidone; D001285:Atropine; C006649:methylatropine; D006220:Haloperidol