0000000000729900
AUTHOR
Marie-luise Buchholzer
Stimulation of hippocampal acetylcholine release by hyperforin, a constituent of St. John’s Wort
Abstract Extracts of the medicinal plant St. John’s Wort ( Hypericum perforatum ) are widely used in the therapy of affective disorders and have been reported to exert antidepressant, anxiolytic, and cognitive effects in experimental and clinical studies. We here report that hyperforin, the major active constituent of the extract, increases the release of acetylcholine from rat hippocampus in vivo as determined by microdialysis. Hippocampal acetylcholine levels were increased by 50–100% following the systemic administration of pure hyperforin at doses of 1 and 10 mg/kg. The effect was almost completely suppressed by local perfusion with calcium-free buffer or with tetrodotoxin (1 μM). We co…
Dual modulation of striatal acetylcholine release by hyperforin, a constituent of St. John's wort.
Extracts of the medicinal plant St. John's wort (Hypericum perforatum) are widely used for the treatment of mild to moderate depression. Hyperforin, a constituent of St. John's wort, is known to inhibit the sodium-dependent uptake of catecholamines and amino acids into synaptic nerve endings, probably by interference with mechanisms controlling the synaptic sodium concentration. Because de novo synthesis of acetylcholine (ACh) is dependent on sodium-dependent high-affinity choline uptake, we studied the effect of hyperforin on choline (Ch) uptake in vitro and on striatal ACh release in vivo using microdialysis. In rat brain synaptosomes, hyperforin inhibited high-affinity choline uptake wit…
Serotonergic modulation of hippocampal acetylcholine release after long-term neuronal grafting
Adult female rats sustained aspirative fimbria-fornix lesions and, 2 weeks later, received intrahippocampal grafts of fetal septal or mixed septal-raphe cell suspensions. Twenty-four months later, the extracellular concentration of hippocampal acetylcholine (ACh) was determined by microdialysis. Basal ACh levels (5-65 fmol/5 microl sham-operated rats) were strongly reduced after lesioning (3-7 fmol/5 microl). In septally transplanted and septal-raphe co-transplanted rats, hippocampal ACh concentrations were restored to near-normal levels (15-25 fmol/5 microl), indicating long-term functional survival of hippocampal transplants. After administration of citalopram (100 microM by infusion) and…
NMDA-induced acetylcholine release in mouse striatum: role of NO synthase isoforms
Striatal cholinergic interneurons are stimulated by glutamatergic inputs from thalamus and cortex via NMDA receptors. The present microdialysis study was designed to characterize the role of nitric oxide (NO) in this process and to identify the NO synthase (NOS) isoform responsible for this effect. For this purpose, we studied the effects of NMDA and 3-morpholino sydnonimine (SIN-1) perfusions on the release of acetylcholine (ACh) in mouse striatum. In wild-type C57/Bl6 mice, perfusion of NMDA (100 µm) induced a two-fold stimulation of ACh release. This effect was attenuated in mice lacking endothelial NOS but was completely absent in mice lacking neuronal NOS. Local perfusion of SIN-1 (300…
Glucose plus choline improve passive avoidance behaviour and increase hippocampal acetylcholine release in mice.
The present study tests the effects of glucose and choline, the biosynthetic precursors of acetylcholine, on passive avoidance behaviour and hippocampal acetylcholine release measured by microdialysis in awake mice. Glucose (10 and 30mg/kg) or choline chloride (6-60mg/kg), given by i.p. injection immediately after training, dose-dependently enhanced retention in an inhibitory avoidance task. Combinations of low doses of glucose (10mg/kg) and choline chloride (20mg/kg) which alone were submaximally effective significantly increased retention latencies in a synergistic manner, an effect which was sensitive to atropine (0.5mg/kg). This beneficial effect vanished when higher doses of glucose or…