ACETYLCHOLINE-RELEASE AND CHOLINE AVAILABILITY IN RAT HIPPOCAMPUS - EFFECTS OF EXOGENOUS CHOLINE AND NICOTINAMIDE

The influence of choline availability on acetylcholine (ACh) release i n the hippocampus of the awake rat was investigated using the microdia lysis procedure. Three treatments enhancing choline availability for b asal and atropine-evoked ACh release were evaluated: acute administrat ion of choline chloride (20 mg/kg i.p.); pretreatment of animals with nicotinamide (10 mmol/kg s.c.) 2 hr before atropine injection and diet ary choline supplementation (5-fold increase of choline intake for 15- 18 days), Although acute choline administration led to a shortlasting (15 min) increase of basal choline efflux by 25% and nicotinamide caus ed a long-lasting (5 hr) increase by 105%, neither one affected basal ACh release. However, basal release of choline (1.38 pmol/min) and of ACh (114 fmol/min) in the hippocampus was slightly increased in cholin e-supplemented animals (choline: 1.92 pmol/min; ACh: 140 fmol/min). In untreated animals, atropine administration caused a 3-fold increase o f ACh efflux that lasted approximately 2.5 hr. All treatments, acute o r chronic choline and nicotinamide, led to significant increases of th e maximum and duration of atropine-evoked ACh release. Total atropine- evoked ACh efflux (area under the curve) was increased 2- to 3-fold, w ith the largest effect evoked by the combination of nicotinamide and c holine. The results clearly demonstrate that, under stimulated conditi ons, hippocampal ACh release could be facilitated when the availabilit y of choline for ACh synthesis was enhanced by dietary or pharmacologi cal means. Under certain conditions, significant effects of increased choline availability on ACh release can be revealed in the absence of an overall increase of extracellular choline.