Intranasal Galanin(1–15) influences depression- and anxiety-related behaviors through sex-dependent mechanisms in rats

This study analyzes, for the first time, the effects of GAL(1–15) on female rats and compares the expression of galaninergic and serotonergic genes between males and females to understand sex-dependent mechanisms in depression.

Methods

For this purpose, the effect of GAL(1–15) administered intranasally in female rats was assessed, using validated behavioral tests for depression: the Forced Swim Test (FST) and the Tail Suspension Test (TST), as well as the anxiety behavior test: the Open Field Test (OFT). Furthermore, the expression of galaninergic genes (GAL, GALR1, GALR2, GALR3) and the 5-HT1A receptor was compared in untreated male and female rats using qPCR in key brain regions implicated in depressive disorder: the dorsal raphe nucleus (DR), the dorsal hippocampus, and the prefrontal cortex (PFC).

Results We demonstrated that GAL(1–15) intranasally administered in female rats strongly produced depressive behavior in the FST as well as in the TST. Moreover, in the anxiety test, intranasal GAL(1–15) at high doses produced anxiety behavior in the OFT. In addition, the qPCR study revealed that naïve female rats exhibited increased expression of the galaninergic system and 5-HT1A receptor compared to naïve male rats in the DR, dorsal hippocampus, and PFC, several nuclei implicated in depression.

Conclusions.These results demonstrate the existence of sexual dimorphism in the galangergic system.These findings on sex-specific neurobiological variations are crucial for advancing toward more precise therapies tailored to the specific characteristics of each sex in the treatment of depression.