Activation of dopamine D1 receptors enhances cholinergic transmission and social cognition: a parallel dialysis and behavioural study in rats.

Full Abstract

Although dopaminergic mechanisms are known to modulate cognitive function and cholinergic transmission, their pharmacological characterization remains incomplete. Herein, the role of D1 sites was evaluated employing neurochemical and behavioural approaches. By analogy to the acetylcholinesterase inhibitor, galantamine (0.0025-0.63 mg/kg s.c.), the selective and high efficacy D1 receptor agonist, SKF 82958, dose-dependently (0.0025-0.63), robustly and potently enhanced extracellular levels of acetylcholine (ACh) in the frontal cortex and hippocampus of freely moving rats. A further agonist, SKF 81297 (0.04-0.63), mimicked this action whereas the selective antagonist, SCH 23390 (0.00063-0.63), decreased levels of ACh. In the presence of SCH 23390 (0.08), the facilitatory influence of SKF 82958 (0.04) upon ACh levels was abolished. In a model of social memory (recognition of a juvenile by an adult rat), galantamine (0.04-0.63), SKF 82958 (0.01-0.16) and SKF 81297 (0.001-0.16) dose-dependently abrogated amnesic effects of the muscarinic receptor antagonist scopolamine (1.25). Further, under conditions of spontaneous loss of recognition, mimicking the effects of galantamine (0.04-2.5), SKF 82958 (0.01-0.16) and SKF 81297 (0.04-1.25) dose-dependently and specifically facilitated social recognition. Conversely, SCH 23390 (0.0025-0.04) exerted a modest negative influence upon social recognition and, in its presence, the pro-cognitive properties of SKF 82958 were blocked. In conclusion, D1 receptors exert a tonic, facilitatory influence upon cholinergic transmission and social recognition. Although the relationship between these actions awaits further clarification, these data underpin the relevance of D1 receptors to CNS disorders in which cholinergic transmission and social cognition are disrupted.

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Author information

Author/s: Di Cara, Benjamin (B); Panayi, Fany (F); Gobert, Alain (A); Dekeyne, Anne (A); Sicard, Dorothée (D); De Groote, Lotte (L); Millan, Mark J (MJ);

Affiliation: Institut de Recherches Servier, Department of Psychopharmacology, 125 chemin de Ronde, 78290 Croissy-sur-Seine, France.

Journal and publication information

Publication Type: Journal Article

Journal: The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP) (Int J Neuropsychopharmacol), published in England. (Language: eng)

Reference: 2007-Jun; vol 10 (issue 3) : pp 383-99

Dates: Created 2007/05/17; Completed 2007/07/20;

PMID: 16925890, status: MEDLINE (last retrieval date: 12/26/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Acetylcholine - metabolism
Animals
Behavior, Animal - physiology
Benzazepines - pharmacology
Cholinesterase Inhibitors - pharmacology
Dopamine Antagonists - pharmacology
Extracellular Space - metabolism
Galantamine - pharmacology
Hippocampus - drug effects; metabolism
Male
Microdialysis

Muscarinic Antagonists - pharmacology
Parasympathetic Nervous System - physiology
Prefrontal Cortex - drug effects; metabolism
Rats
Rats, Wistar
Receptors, Dopamine D1 - agonists; antagonists & inhibitors
Receptors, Muscarinic - drug effects; physiology
Recognition (Psychology) - drug effects; physiology
Scopolamine - pharmacology
Social Behavior
Synaptic Transmission - physiology

Associated Chemicals: Benzazepines (0) ; Cholinesterase Inhibitors (0) ; Dopamine Antagonists (0) ; Muscarinic Antagonists (0) ; Receptors, Dopamine D1 (0) ; Receptors, Muscarinic (0) ; Galantamine (357-70-0) ; Scopolamine (51-34-3) ; Acetylcholine (51-84-3) ; SK&F 81297 (71636-61-8) ; SK&F 82958 (80751-65-1)

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