The effects of the adenosine reuptake inhibitor soluflazine on synaptic potentials and population hypoxic depolarizations in area CA1 of rat hippocampus in vitro

• Published in: Neuropharmacology Vol. 32; no. 2; pp. 149 - 155
• Main Authors: Boissard, C.G., Gribkoff, V.K.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.02.1993; Elsevier
• Subjects: adenosine; Adenosine - metabolism; adenosine reuptake inhibitor; Animals; Biological and medical sciences; Cardiovascular system; hippocampal slices; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - metabolism; hypoxia; Hypoxia, Brain - metabolism; Hypoxia, Brain - physiopathology; In Vitro Techniques; Male; Medical sciences; Pharmacology. Drug treatments; Piperazines - pharmacology; Rats; Rats, Inbred F344; soluflazine; Synapses - drug effects; Synaptic Transmission - drug effects; Theophylline - analogs & derivatives; Theophylline - pharmacology; Vasodilator agents. Cerebral vasodilators; adenosine; hypoxia; hippocampal slices; adenosine reuptake inhibitor; soluflazine; Nervous system diseases; Adenosine; Rat; Treatment efficiency; Rodentia; Electrophysiology; Cardiovascular disease; In vitro; Biological activity; Vertebrata; Chemotherapy; Experimental disease; Mammalia; Ischemia; Neuromodulator; Animal; Antiïschemic; Excitatory postsynaptic potential; Cerebrovascular disease; Brain (vertebrata)
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/0028-3908(93)90095-K

Adenosine has recently been shown to play a potentially important role in the regulation of synaptic excitability during experimental hypoxia in the hippocampus of the rat. Endogenous adenosine, rapidly released at the initiation of a hypoxic episode, produced synaptic depression, which could protect sensitive neurons. In the present experiments, an inhibitor of the reuptake of adenosine, soluflazine (R64719) was employed to increase the levels of endogenous adenosine under normoxic and hypoxic conditions in slices of the hippocampus of the rat. Soluflazine produced a slow-onset, concentration-dependent depression of population excitatory postsynaptic potentials, which was reversed by the specific A 1 adenosine receptor antagonist, 8-cyclopentyltheophylline. During severe N 2-induced hypoxia, soluflazine significantly delayed hypoxic depolarization. These results suggest that inhibition of the reuptake of adenosine may have therapeutic potential in the amelioration of hypoxic/ischemic neuronal damage, particularly in the hippocampus.