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  • Title: Blockade of dorsal hippocampal dopamine receptors inhibits state-dependent learning induced by cannabinoid receptor agonist in mice.
    Author: Zarrindast MR, Dorrani M, Lachinani R, Rezayof A.
    Journal: Neurosci Res; 2010 May; 67(1):25-32. PubMed ID: 20144666.
    Abstract:
    To clarify the interaction between cannabinnoid CB1 receptors and the dopaminergic system in memory processes, the effects of dopamine receptor agents on the state-dependent learning induced by the non-selective CB1/CB2 receptor agonist, WIN55,212-2 have been investigated in mice. Animals implanted with unilateral cannula at the CA1 region of the dorsal hippocampus and microinjected with WIN55,212-2 and/or dopaminergic agents, were tested using a single-trial step-down passive avoidance task. Intra-CA1 microinjections of WIN55,212-2 (0.1-1 microg/mouse) immediately after training, decreased the step-down latency, indicating an amnesic effect of the drug. The amnesia was reversed by pre-test administration of the drug, suggesting state-dependent learning by the cannabinoid. Pre-test microinjection of apomorphine, a D1/D2 dopamine receptor agonist (0.1-0.3 microg/mouse) into the CA1 region reversed the amnesia induced by post-training WIN55,212-2 (1 microg/mouse). Moreover, pre-test co-administration of apomorphine with an ineffective dose of WIN55,212-2 (0.01 microg/mouse), showed a reversion of the impairment on retention performance. Pre-test administration of the same doses of apomorphine did not show any response by itself. Pre-test intra-CA1 administration of a D1 dopamine receptor antagonist, SCH23390 (0.05-0.3 microg/mouse) or D2 dopamine receptor antagonist, sulpiride (0.125-0.5 microg/mouse) inhibited the expression of WIN55,212-2-induced state-dependent learning. Pre-test microinjection of the same doses of SCH23390 or sulpiride had no effect on WIN55,212-2-induced amnesia. Moreover, single injection of SCH23390 (0.2 and 0.3 microg/mouse) or sulpiride (0.125 microg/mouse) decreased memory retrieval. The results suggest that the dorsal hippocampal dopaminergic system participates in the modulation of WIN55,212-2-induced state-dependent learning.
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