Dopamine D1 and D2 receptor agents and their interaction influence the synaptic density of the rat prefrontal cortex

Recent findings indicate that some monoamines contribute to synaptic maintenance. We examined the synaptic density of the prefrontal cortex of rats with the single or combined administration of D1 and D2 antagonists and agonists. When each agent was administered individually, we observed a significant difference in synaptic density. This indicates that dopamine regulates synaptic maintenance. With the combined administration of antagonists or agonists at high dosages, a synergistic effect was observed. With the combined administration of a D1 antagonist and D2 agonist or a D1 agonist and D2 antagonist, a low dose of the D2 receptor drug enhanced the effect of the D1 receptor drug. The D1 receptor drug offset the effect of the high dose of D2 receptor drug, suggesting the possibility that the D1 receptor family is essential for synaptic maintenance.