Effect of cholinergic activation by physostigmine on working memory failure caused in rats by pharmacological manipulation of hippocampal glutamatergic and 5-HTergic neurotransmission.
The muscarinic receptor antagonist scopolamine significantly increased the number of errors in the working memory task with a three-panel runway setup, when injected bilaterally at 3.2 micrograms/side into the dorsal hippocampus. The increase in working memory errors induced by intrahippocampal 3.2 micrograms/side scopolamine was reduced by concurrent injection of the cholinesterase inhibitor physostigmine (1.0 and 3.2 micrograms/side. However, physostigmine (3.2 micrograms/side) did not affect an increase in working memory errors induced by intrahippocampal injection of the competitive N-methyl-D-aspartate (NMDA) receptor antagonist (+/)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) at 32 ng/side. Likewise, physostigmine (3.2 micrograms/side) was ineffective in reducing an increase in working memory errors caused by intrahippocampal administration of the 5-hydroxytryptamine1A (5-HT1A) receptor agonist (+/-)-8-hydroxy-2-(di-n-pro-pylamino)tetralin (8-OH-DPAT) at 10 micrograms/side. These results suggest that the septohippocampal cholinergic activity is necessary for normal working memory processes, but that cholinergic activation neither compensates loss of hippocampal NMDA receptor-mediated neurotransmission nor counteracts the overstimulation of hippocampal 5-HT1A receptors in terms of working memory function.
Ohno
M
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Kishi
A
A
Watanabe
S
S
D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D008570:Memory, Short-Term / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine / Q000037:antagonists & inhibitors; D012701:Serotonin / Q000502:physiology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*
D002800:Cholinesterase Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018727:Muscarinic Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D018698:Glutamic Acid; D010830:Physostigmine; D012601:Scopolamine; D000109:Acetylcholine