Inhibitory effects of group II mGluR-related drugs on memory performance in mice

The cAMP/protein kinase A signaling pathway is negatively modulated by group II metabotropic glutamate receptors (mGluRs), and the cross-talk that occurs between these receptors may modulate learning and memory. To examine the relationship among cAMP/PKA-signaling pathway activity, group II mGluRs,...

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Bibliographic Details
Published in:Physiology & behavior 2004-02, Vol.80 (5), p.747-758
Main Authors: Sato, Tomoaki, Tanaka, Koh-ichi, Ohnishi, Yoshiko, Teramoto, Toyonori, Irifune, Masahiro, Nishikawa, Takashige
Format: Article
Language:English
Subjects:
Amino Acids - pharmacology
Animal
Animals
Anticonvulsants - pharmacology
Avoidance Learning - drug effects
Behavioral psychophysiology
Biological and medical sciences
cAMP
Colforsin - pharmacology
Cyclic AMP - physiology
Cyclic AMP-Dependent Protein Kinases - drug effects
Cyclopropanes - pharmacology
Dose-Response Relationship, Drug
Enzyme Inhibitors - pharmacology
Excitatory Amino Acid Antagonists - pharmacology
Fundamental and applied biological sciences. Psychology
Glycine - analogs & derivatives
Glycine - pharmacology
Isoquinolines - pharmacology
Learning
Learning. Memory
Male
Memory
Memory - drug effects
Metabotropic glutamate receptor agonist
Metabotropic glutamate receptor antagonist
Metabotropic glutamate receptors
Mice
Neurotransmission and behavior
Psychology. Psychoanalysis. Psychiatry
Psychology. Psychophysiology
Reaction Time - drug effects
Receptors, Metabotropic Glutamate - agonists
Receptors, Metabotropic Glutamate - antagonists & inhibitors
Receptors, Metabotropic Glutamate - drug effects
Rolipram - pharmacology
Signal Transduction - drug effects
Sulfonamides
Tetradecanoylphorbol Acetate - pharmacology
Xanthenes - pharmacology
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Summary:The cAMP/protein kinase A signaling pathway is negatively modulated by group II metabotropic glutamate receptors (mGluRs), and the cross-talk that occurs between these receptors may modulate learning and memory. To examine the relationship among cAMP/PKA-signaling pathway activity, group II mGluRs, and learning and memory, mice were trained to perform a step-through-type passive avoidance task, and 10 min before each avoidance trial the following drugs were injected intracisternally (i.cist.): vehicle (0.05% dimethylsulfoxide); a specific group II mGluR agonist, DCG-IV (1–50 ng/mouse); a specific group II mGluR antagonist, LY341495 (10–300 ng); a selective inhibitor of cAMP-specific phosphodiesterase, rolipram (100–1000 ng); an activator of adenylyl cyclase, forskolin (25–250 ng); a specific inhibitor of PKA, H-89 (150 or 300 ng) or; an activator of protein kinase C, phorbol 12-myristate 13-acetate (PMA 200 ng). DCG-IV (25 and 50 ng) or LY341495 (150 and 300 ng) reduced the latency in the avoidance task. The reduction of latency by DCG-IV was not observed in mice coinjected with DCG-IV (50 ng) together with rolipram (500 ng) or forskolin (25 ng). Conversely, coinjection of LY341495 with 100 or 1000 ng rolipram, or with 25 or 250 ng forskolin tended to potentiate the LY341495-induced shortening of latency. In addition, the reduction of latency by DCG-IV (50 ng) was not observed in mice coinjected with DCG-IV and PMA together. However, the reduction of latency by LY341495 (300 ng) was potentiated when the drug was coadministered with PMA. These results suggest that changes in the cAMP/PKA-signaling pathway, mediated by group II mGluRs, influence memory in the passive avoidance task, and that both the excessive activation and deactivation of this pathway may induce the impairment of learning and memory.
ISSN:0031-9384
1873-507X
DOI:10.1016/j.physbeh.2003.12.010