Anti-Anxiety Effects of Prelimbic 5-HT4 Receptors in the Rat Model of Parkinson’s Disease: Evidence from Behavioral and Electrophysiological Study

Abstract

Objective: Clinical and laboratory studies have demonstrated that prelimbic (PrL) and serotonin-4 (5-HT4) receptors may have the key role in regulating anxiety. However, the pathophysiology of anxiety in Parkinson’s disease (PD) remains obscure. In this research, the effects of PrL 5-HT4 receptors on anti-anxiety behaviors in hemiparkinsonian rats were investigated. Methods: PD model rats were used as the research subjects, starting with behavioral changes, from the point of view of electrophysiology, the regulatory effect of PrL 5-HT4 receptors on PD-related anxiety and the possible mechanism were explored. Results: Anxiety-like behaviors were induced via MFB lesion in rats. Intra-PrL injection of 5-HT4 receptors agonist RS67333 induced anti-anxiety effects in both sham and PD group. In the sham group, PrL administration of 5-HT4 receptors antagonist SB204070 produce anti-anxiety effects, but in the PD group, the expression of anxiety-like behavior was increased. Compared to the sham group, the effective dose of the behavioral effects of the two drugs in the PD group was obviously higher. Electrophysiological data suggested that PrL administration of RS67333 (SB204070) increased (decreased) the ?ring activities of ?-aminobutyric acid (GABA) neurons in both groups. Compared with rats in sham group, lesioned rats had a shorter duration of the excitation (inhibition) effects on firing activities of GABA neurons. Conclusion: PrL 5-HT4 receptors regulate anxiety behaviors in PD rats, and its mechanism may be related to the down-regulation of expression or function of PrL 5-HT4 receptors in PD.