Chronic Nasal Administration of Kisspeptin-54 Regulates Mood-Related Disorders Via Amygdaloid GABA in...

Depression and anxiety, the most prevalent neuropsychiatric manifestations in Parkinson’s disease (PD), negatively impact their quality of life.

To determine whether the chronic nasal administration of kisspeptin-54 (KP-54) could. Alleviate symptoms of anxiety and depression in hemi-Parkinsonian rats.

Experimental study.

This study included adult Sprague Dawley male rats who were administered either a vehicle (artificial cerebrospinal fluid) or 6-hydroxydopamine (6-OHDA) unilaterally into the medial forebrain bundle. The vehicle, or KP-54 (3 nmol/kg, applied topically to the rhinarium), was administered daily for a seven-day period. The sucrose preference test (SPT), elevated plus maze test (EPMT), and open field test (OFT) were implemented to evaluate depression- and anxiety-like behaviors, respectively, seven days following the lesion surgery. Gamma-aminobutyric acid (GABA) concentrations in the amygdala were quantified using mass spectrometry. Tyrosine hydroxylase in substantia nigra was analyzed using immunohistochemistry.

The nasal delivery of KP-54 significantly reduced depressionand anxiety-like behaviors that were induced by 6-OHDA, as indicated by the results of the SPT, OFT, and EPMT. Moreover, it was observed that nasal KP-54 effectively mitigated 6-OHDA-induced motor deficits and the loss of nigral dopaminergic neurons. The nasal administration of KP-54 augmented the decline in GABA levels in the amygdala induced by 6-OHDA. Furthermore, effective correlations were established between GABA concentrations and behavioral parameters.

The nasal delivery of KP-54 could function as a viable therapeutic alternative for treating mood-related disorders in PD.