Effects of dopaminergic and adrenergic blockade on amphetamine-induced extravasation of protein into the brain of normotensive and spontaneously hypertensive rats

Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats were given saline or amphetamine sulfate (2.5 or 5.0 mg/kg). The amphetamine caused an increased extravasation of ¹¹³I-labelled serum albumin (RISA) into the brain across the blood-brain barrier (BBB) which was associated directly with the change in the systemic blood pressure. Premedication with the dopaminergic blocking agents, haloperidol (2 mg/kg) or domperidone (6 mg/kg) blocked both the extravasation of the RISA and the elevation of the blood pressure caused by amphetamine. Premedication with the alpha adrenergic blocking agent, phentolamine (3 mg/kg), or with the beta adrenergic blocking agent, propranolol (2 mg/kg) both greatly increased the permeability of the blood-brain barrier to RISA and decreased the blood pressure in hypertensive animals only. Both of these blocking agents also prevented the increased extravasation of RISA caused by amphetamine. These results indicate that movement of large molecules, such as RISA, across the blood-brain barrier can be increased independent of increases in the systemic blood pressure in hypertensive rats.