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The effects of dietary choline availability on the transport of choline across the blood-brain barrier (BBB) were investigated using the intracarotid injection technique. Maintenance of rats on choline-deficient, basal choline, or choline-supplemented diets for 28-32 days led to respective increases in blood levels of choline and correlative increases in the velocity of transport of choline measured using a buffer injectate. When serum from these rats was included in the injectate and transport determined in control animals, there was a marked inhibition of choline transport that was related to the concentration of choline in the diets. Results suggest that the activity of the choline carrier at the BBB is antagonized by an inhibitory substance in serum whose concentration or activity may be modified by chronic alterations in circulating levels of choline and whose presence may normally regulate the velocity of choline transport.

The actions of the anticonvulsants phenobarbital, ethosuximide and carbamazepine were examined electrophysiologically at the frog neuromuscular junction. Phenobarbital reduced miniature end-plate potential (MEPP) amplitude, did not significantly affect end-plate potential amplitude and increased quantal content. Ethosuximide decreased MEPP and end-plate potential amplitudes proportionally; quantal content was unchanged. Carbamazepine decreased end-plate potential amplitude more than MEPP amplitude; quantal content was decreased. In a solution containing elevated (7.5 mM) K+, phenobarbital and carbamazepine increased MEPP frequency, whereas ethosuximide had no effect. Carbamazepine had to be dissolved in a solvent, propylene glycol, which was shown to produce small, but sometimes statistically significant, alterations in the measured parameters of neuromuscular transmission. The results show that all three of these anticonvulsants depress postjunctional sensitivity to released acetylcholine producing parallel dose-response curves for MEPP amplitude inhibition. These experiments also show that these drugs exhibit different mechanisms of action with respect to nerve-stimulated neurotransmitter release from nerve terminals at the neuromuscular junction: phenobarbital enhances acetylcholine release, ethosuximide has no effect and carbamazepine decreases transmitter release.

The effect choline (60 mg/kg, i.p.) on fluphenazine- and pentylenetetrazol-induced alterations in the concentration of acetylcholine (ACh) and/or the rate of sodium-dependent high-affinity choline uptake (HACU) in rat striatum and hippocampus was studied. Systemic administration of the dopamine receptor blocking agent fluphenazine hydrochloride (.05 mg/kg, i.p.) decreased the concentration of ACh in the striatum; this effect was prevented by the prior administration of choline. The central nervous system stimulant pentylenetetrazol (30 mg/kg, i.p.) reduced the concentration ACh in both striatum and hippocampus and increased the velocity of HACU in the hippocampus. Pretreatment with choline totally prevented the depletion of ACh induced by pentylenetetrazol in the striatum. In the hippocampus, prior administration of choline prevented the pentylenetetrazol-induced increase in the rate of HACU and attenuated the effect of pentylenetetrazol on the levels of ACh. Results indicate that the acute administration of choline antagonizes pharmacologically induced alterations in cholinergic activity as assessed by the rate of HACU and the steady-state concentration of ACh. Furthermore, data support the hypothesis that the administration of choline increases the ability of central cholinergic neurons to synthesize ACh under conditions of increased neuronal activity.

The effect of chronic choline supplementation was studied on the toxicity of various pharmacological agents in rats and mice. Choline prevented both the incidence of seizures and the consequent lethality of nicotine, paraoxon, pentylenetetrazol, and strychnine. Nicotine toxicity was most markedly affected, and the prophylactic effects of choline were present in both rats and mice following either dietary or parenteral supplementation. Results suggest that chronic choline availability may alter neuronal membrane excitability.