Transfer of [ 3H]leucine across the blood-brain barrier at high blood-side oxytocin concentrations in normal and morphine-dependent rats

Abstract

The effects of circulating oxytocin on permeability of the blood-brain barrier (BBB) to L-[ 3H]leucine were studied in anaesthetized rats using the intracarotid, single pass, bolus injection technique. After bolus intracarotid oxytocin injection (10 −9M), there were no differences in [ 3H]leucine uptake, compared with controls, in any of eight brain regions with a ‘tight’ BBB (olfactory bulb, frontal cortex, visual cortex, corpus striatum, hippocampus, thalamus, hypothalamus and colliculi) or in BBB-free, ‘leaky’ structures (pineal gland, choroid plexus, neuro-intermediate pituitary, anterior pituitary). [ 3H]leucine uptake by the ‘leaky’ structures was 2.4x and 2.6x uptake by ‘tight’ regions in the oxytocin and control groups respectively. In morphine-dependent rats, naloxone increased oxytocin secretion 28-fold within 5 min, but did not affect [ 3H]leucine uptake for any BBB-protected brain region or BBB-free ‘leaky’ structure. Accumulation of [ 3H]leucine was 8.3x and 7.0x greater in the ‘leaky’ structures than in the ‘tight’ regions in the naloxone and control groups respectively; [ 14C]inulin accumulation by each ‘tight’ region (measured simultaneously with [ 3H]leucine to determine the vascular space) was not affected by naloxone. It is concluded that even very high blood plasma concentrations of oxytocin do not affect BBB permeability for leucine. It is unlikely that altered BBB permeability, at least for amino acids, contributes to CNS changes during naloxone-provoked morphine withdrawal.