Summary
Amphetamine administration to rats anaesthetized with nitrous oxide resulted in protein extravasation in the brain, particularly in the frontoparietal cortex. The drug is known to increase the cerebral blood flow in the same areas, indicating a vasodilatory action on the cerebral vessels. Protein leakage could be prevented by lowering the blood pressure and, to a large extent, also by hyperventilation. This suggests that the permeability disturbance is caused by the mechanical stress which results from high intraluminal pressure in combination with vasodilatation.
The pharmacological effect of amphetamine is caused by a catecholamine release in the central nervous system and in the periphery. The vasodilatory effect of amphetamine could be either a direct effect on the cerebral vessels or could be secondary to an increased cerebral metabolism. The vasodilatory betaadrenergic receptors in the cerebral vessels are of beta1 type. Practolol, a selective beta1-receptor antagonist which can prevent the vasodilatory effect of isoprenaline on cerebral vessels, did not influence the amphetamine induced protein leakage. In contrast, propranolol, a non-selective beta-receptor blocking drug which earlier has been shown to prevent catecholamine induced increase of CBF and oxygen consumption, diminished or prevented the protein leakage. It is likely that the cerebral vasodilatation caused by amphetamine, at least in part, is secondary to an increased cerebral metabolism induced by a catecholamine release.
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Carlsson, C., Johansson, B.B. Blood-brain barrier dysfunction after amphetamine administration in rats. Acta Neuropathol 41, 125–129 (1978). https://doi.org/10.1007/BF00689763
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DOI: https://doi.org/10.1007/BF00689763