title: Cholinergic and dopaminergic agents which inhibit a passive avoidance response attenuate the paradigm-specific increases in NCAM sialylation state.
abstract: The influence of cholinergic and dopaminergic agents on the acquisition of a passive avoidance response in the rat is demonstrated. Trifluoperazine (0.12 mg/kg), a dopamine antagonist, inhibited task acquisition when present during training or later, during consolidation, at the 10-12 h post-training period and at no other intervening time point. Induction of amnesia was dose-dependent and was not apparent when the dose exceeded 0.12 mg/kg. This effect appears to be due to an increase in dopamine release through presynaptic receptor antagonism as similar results could be obtained by the administration of apomorphine (0.5 mg/kg), a dopamine agonist, and this effect could be antagonized by the D1 receptor selective antagonist SCH-23390. Scopolamine (0.15 mg/kg), a muscarinic antagonist, impaired acquisition of the passive avoidance response when administered during training and, separately, at the 6 h post-training period. This could not be attributed to presynaptic antagonism as oxotremorine (0.2 mg/kg), a muscarinic agonist, had no amnesic action. Administration of apomorphine or scopolamine during training and at the appropriate post-training period prevented subsequent paradigm-specific increases of neural cell adhesion molecule sialylation state in hippocampal immunoprecipitates obtained at 24 h after task acquisition and 4 h following intraventricular infusion of the labelled sialic acid precursor - N-acetyl-D-mannosamine. Oxotremorine alone did not influence neural cell adhesion molecule sialylation state. These observations provide further evidence of a regulatory role for neural cell adhesion molecule sialylation state in information storage processes.
authors.affiliation: Department of Pharmacology, University College, Belfield, Dublin, Ireland.
authors.forename: E
authors.initials: E
authors.lastname: Doyle
authors.forename: C M
authors.initials: CM
authors.lastname: Regan
mesh_terms: D000647:Amnesia / Q000139:chemically induced; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D006003:Glycogen / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D015151:Immunoblotting; D008297:Male; D008568:Memory / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D019158:N-Acetylneuraminic Acid; D010277:Parasympathomimetics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012794:Sialic Acids / Q000378:metabolism*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D015259:Dopamine Agents; D010277:Parasympathomimetics; D012794:Sialic Acids; D006003:Glycogen; D019158:N-Acetylneuraminic Acid