Dopamine D_1 Agonist Facilitates Long‐term Depression Induction by Callosal Low‐frequency Stimulation in Rat Anterior Cingulate Cortex

概要

論文の詳細を見る
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