ARECOLINE, BUT NOT HALOPERIDOL, INDUCES CHANGES IN THE PERMEABILITY OF THE BLOOD-BRAIN-BARRIER IN THE RAT

Abstract— The aim of the present study was to investigate the existence of alterations of the blood‐brain barrier (BBB) permeability in rats injected with centrally acting drugs, by calculating a unidirectional blood‐to‐brain transfer constant (Ki) for the circulating tracer [14C]‐α‐aminoisobutyric acid. The intraperitoneal (i.p.) injection of the dopaminergic antagonist haloperidol (1 mg kg−1) did not modify the regional BBB permeability. When the cholinomimetic agent arecoline hydrobromide (6.25 mg kg−1) was injected i.p. into methylatropine‐pretreated rats, it induced a significant decrease of Kj values within the frontal cortex, parietal cortex, striatum and brain‐stem. Our findings emphasize two concepts: (1) centrally acting drugs, such as arecoline, can induce changes in the BBB permeability, through several mechanisms; (2) there is no predictable correlation of drug stimulation of specific brain neuronal pathways and changes in the permeability of the BBB. 1990 Royal Pharmaceutical Society of Great Britain