In Vivo Effect of a 5-HT(7) Receptor Agonist on 5-HT Neurons and GABA Interneurons in the Dorsal Raphe Nuclei of Sham and PD Rats.

The 5-hydroxytryptamine (5-HT; serotonin) neurotransmission is severely affected by the degeneration of nigrostriatal dopaminergic neurons. Here, we report the effects of the systemic administration of the 5-HT(7) receptor agonist AS-19. In sham rats, the mean response of the 5-HT neurons in the dorsal raphe nucleus (DRN) to systemic AS-19 was excitatory and the mean response of the γ-aminobutyric acid (GABA) interneurons was inhibitory. In Parkinson disease (PD) rats, the same dose did not affect the 5-HT neurons and only high doses (640 μg/kg intravenous) were able to the increase GABA interneuron activity. These results indicate that DRN 5-HT neurons and GABA interneurons are regulated by the activation of 5-HT(7) receptors and that the degeneration of the nigrostriatal pathway leads to decreased responses of these neurons to AS-19, which in turn suggests that the 5-HT(7) receptors on 5-HT neurons and GABA interneurons in PD rats are dysfunctional and downregulated.