title: The contribution of adenosine to paired-pulse inhibition in the normal and disinhibited hippocampal slice.
abstract: The effects of the adenosine receptor antagonist 1,3-dimethyl-8-cyclopentylxanthine (cyclopentyltheophylline) and the enzyme adenosine deaminase have been examined on paired-pulse inhibition between orthodromic evoked field potentials in the CA1 region of the normal and disinhibited hippocampal slice. In the presence of the GABAA receptor antagonist (-)-bicuculline methobromide, cyclopentyltheophylline suppressed homosynaptic paired-pulse inhibition between stimuli 300 ms apart. Slices treated with (-)-bicuculline and cyclopentyltheophylline together tended to develop spontaneous burst potentials. In slices in which a surgical cut isolated the CA1 and CA3 areas, thereby preventing the development of bursts in CA1, the effect on paired-pulse inhibition was lessened but was still apparent. Adenosine deaminase, in the presence of (-)-bicuculline showed the same effect as cyclopentyltheophylline, decreasing substantially the amount of paired-pulse inhibition. These results suggest that adenosine may contribute to homosynaptic paired-pulse inhibition in disinhibited slices. For comparison, we also examined the effect of cyclopentyltheophylline in normal ((-)-bicuculline-free) slices. At 100 nM, cyclopentyltheophylline increased reversibly the size of orthodromically evoked synaptic population potentials in the CA1 region of the slices and also reduced reversibly the degree of homosynaptic paired-pulse inhibition between two stimuli delivered only 30 ms apart. This suggests that adenosine may also contribute to shorter latency paired-pulse inhibition in the normal hippocampal slice.
authors.affiliation: Division of Neuroscience and Biomedical Systems, West Medical Building University of Glasgow, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Higgins
authors.forename: T W
authors.initials: TW
authors.lastname: Stone
mesh_terms: D000241:Adenosine / Q000502:physiology*; D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D058892:Adenosine Deaminase Inhibitors; D000697:Central Nervous System Stimulants; D058915:Purinergic P1 Receptor Antagonists; C053907:8-cyclopentyl-1,3-dimethylxanthine; D013806:Theophylline; D000241:Adenosine; D001640:Bicuculline