Leakage of Catecholamines From Rabbit Cerebrospinal Fluid Following Intracerebroventricular Injection

Abstract

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.

Correlation of Neurokinin (NK) 1 Receptor Occupancy in Gerbil Striatum with Behavioral Effects of NK1 Antagonists

“…Although there is evidence that nonpenetrant compounds administered i.c.v. can diffuse from the CNS into the periphery (Anderson et al, 1977;Maccarrone et al, 1983;Kujacic and Carlsson, 1994), it is often questioned whether an i.c.v. injection increases the brain penetration of peripherally administered compounds.…”

“…There are studies reporting leakage of non-CNS-penetrant compounds into the periphery after i.c.v. administration (Anderson et al, 1977;Maccarrone et al, 1983;Kujacic and Carlsson, 1994). It is conceivable that a compound administered peripherally could leak into the CNS through a needle puncture in the BBB caused by the i.c.v.…”