Activation of prelimbic 5-HT1A receptors produces antidepressant-like effects in a unilateral rat model of Parkinson’s disease

• Unilaterally lesioning the medial forebrain bundle in rats induced the depressive-like behaviors.
• Intra-prelimbic cortex of 5-HT1A agonist produced antidepressant effects in sham and lesioned rats.
• Intra-prelimbic cortex of 5-HT1A antagonist produced depressive responses in two groups of rats.
• The doses producing these changes in lesioned rats were higher than those in sham rats.
• The lesion decreased 5-HT1A receptor expression on neuronal glutamate transporter EAAC1-ir neurons in the prelimbic cortex.

Depression is a common symptom in Parkinson’s disease (PD), but its pathophysiology remains unclear. Several lines of studies have revealed that the prelimbic (PrL) sub-region of the ventral medial prefrontal cortex and 5-HT1A receptors are involved in the regulation of depression. In this study, we examined whether complete unilateral lesions of the medial forebrain bundle (MFB) using 6-hydroxydopamine in rats are able to induce depressive-like behaviors, the role of PrL 5-HT1A receptors in the regulation of these behaviors, and co-localization of 5-HT1A receptor and neuronal glutamate transporter EAAC1-immunoreactive (EAAC1-ir) neurons in the PrL. The MFB lesions induced depressive-like responses as measured by the sucrose preference and forced swim tests when compared to sham-operated rats. The intra-PrL injection of 5HT1A receptor agonist 8-OH-DPAT (50, 100, and 500 ng/rat) increased sucrose consumption, and decreased immobility time in both sham-operated and the lesioned rats, indicating the induction of antidepressant effects. Furthermore, the intra-PrL injection of 5HT1A receptor antagonist WAY-100635 (60, 120, and 240 ng/rat) showed a decrease in sucrose consumption, and an increase in immobility time, indicating the induction of depressive-like responses. However, the effective doses in the lesioned rats were higher than those in sham-operated rats, which attribute to down-regulation of 5-HT1A receptor expression on EAAC1-ir neurons in the PrL of the lesioned rats. These findings suggest that unilateral lesions of the MFB in rats may induce depressive-like behaviors, and 5-HT1A receptors of the PrL play an important role in the regulation of these behaviors.