Dopamine D_1 Agonist Facilitates Long‐term Depression Induction by Callosal Low‐frequency Stimulation in Rat Anterior Cingulate Cortex
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Dopamine is known to play roles in the processing of emotion. To test whether dopamine has effects on synaptic plasticity in emotion-processing areas, I examined callosally-evoked field potentials in coronal slices of rat anterior cingulate cortex (ACC) when low-frequency stimulation (LFS )was applied to corpus callosum as a conditioning stimulus. Neither dopamine nor the D_2 agonist, quinpirole, had a significant effect on synaptic plasticity, while the D_1 agonist, SKF-38393, facilitated induction of long-term depression (LTD). This facilitative effect of SKF-38393 was completely blocked by the D_1 antagonist, SCH-23390. LFS-induced LTD was not blocked by application of the metabotropic glutamatergic receptor antagonist, MCPG or the voltage-gated calcium channel blocker, nifedipine, but was blocked by application of the N-methyl-D-aspartate receptor (NMDAR) antagonist, APV. The facilitative effect of SKF-38393 on LTD induction was not mimicked by forskolin, an adenylcyclase activator, but was partially mimicked by phorbol 12, 13-didecanoate, which is known to activate the intracellular PKC pathway. These findings suggest that LTD in ACC is induced via NMDAR and facilitated by D_1 agonists at least in part via the PKC-related intracellular pathway. This type of facilitation of LTD induction may be related to the pathogenesis of schizophrenia or major depression, in which frontal lobe hypofunction has been indicated.
- 2011-03-01
論文 | ランダム
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