Leakage of catecholamines from rabbit cerebrospinal fluid following intracerebroventricular injection

The intracerebroventricular (i.c.v.) injection of (-)-isoprenaline and the selective beta 1-adrenoceptor agonist, RO363, elicited reproducible dose-related increases in heart rate in unanaesthetized and anaesthetized rabbits. (-)-Isoprenaline produced vasodepressor effects in unanaesthetized animals, whereas both catecholamines decreased blood pressure in anaesthetized rabbits. Pretreatment with guanethidine sulphate (5 mg/kg i.v.) reduced but did not abolish the tachycardia elicited by i.c.v. RO363, whereas heart rate responses to i.c.v. (-)-isoprenaline were unaffected. Pretreatment of anaesthetized rabbits with hexamethonium bromide (10 mg/kg i.v.) did not markedly affect the tachycardia elicited by i.c.v. RO363 and reduced the response to i.c.v. (-)-isoprenaline in only one out of five experiments. The results suggest that there is a marked leakage of centrally administered catecholamines into the peripheral circulation and that the rabbit may be unsuited for examining centrally mediated cardiovascular effects of catecholamines.