Purine modulation of dizocilpine effects on spontaneous alternation.
The Y-maze was used to assess spontaneous alternation behaviour in mice to examine possible interactions between the N-methyl-D-aspartate receptor channel blocker dizocilpine and purine receptor agonists and antagonists. Scopolamine reduced spontaneous alternation. Dizocilpine also produced a dose-dependent reduction in alternation scores, which was accompanied by an increase in locomotion. The selective A1 adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (CPX) had no effect when administered alone, or in combination with scopolamine. However, when co-administered with dizocilpine, CPX reversed both the deficit in alternation behaviour and also the increase in locomotion induced by dizocilpine. The A1 selective agonist N6-cyclopentyladenosine (CPA) had no effect on either locomotion or alternation scores when administered alone, but in combination with scopolamine, CPA attenuated the scopolamine-induced deficit. CPA had no significant effect on the dizocilpine-induced deficit. The A2 selective agonist N6-[2-(3, 5-dimethoxyphenyl)-2(2-methylphenyl)-ethyl]adenosine (DPMA), had no effect on spontaneous alternation when administered alone, but did cause a depression of locomotion. DPMA had no significant effect when co-administered with scopolamine, but reversed the deficit in spontaneous alternation, and the increase in locomotion induced by dizocilpine. The A2 selective antagonist 3,7-dimethyl-1-propargylxanthine (DMPX) had no effect when given alone or in combination with scopolamine, but when co-administered with dizocilpine, DMPX reversed the reduction in spontaneous alternation caused by dizocilpine. It is concluded that dizocilpine has a detrimental effect on spontaneous alternation which is mediated partly by A1 and A2 adenosine receptors.
Fraser
C M
CM
Division of Neuroscience and Biomedical Systems, University of Glasgow, UK.
Fisher
A
A
Cooke
M J
MJ
Thompson
I D
ID
Stone
T W
TW
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D051379:Mice; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D018047:Receptors, Purinergic P1 / Q000187:drug effects*; D012601:Scopolamine / Q000494:pharmacology*; D014970:Xanthines / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D018727:Muscarinic Antagonists; D018047:Receptors, Purinergic P1; D014970:Xanthines; C048599:N(6)-cyclopentyladenosine; D016291:Dizocilpine Maleate; C051360:1,3-dipropyl-8-cyclopentylxanthine; D012601:Scopolamine; D000241:Adenosine