INTRANASAL EFFECTS OF GALANIN 1-15 ON MOOD DISORDERS AND ALCOHOL SELF-ADMINISTRATION IN RATS

Galanin (GAL) is a 29-amino-acid neuropeptide widely distributed in the central nervous system (CNS). Its N-terminal fragment, GAL(1-15), plays an important role in mood modulation, inducing depressive and anxiogenic-like effects while enhancing the antidepressant efficacy of the 5-HT1A receptor agonist 8-OH-DPAT in the Forced Swim Test (FST). In Alcohol Use Disorder (AUD), our research has shown that GAL(1-15) significantly reduces ethanol preference in the two-bottle-choice test, and decreases alcohol self-administration in an operant model.
To date, GAL(1-15) has only been administered intracerebroventricularly (ICV) in animal studies. Therefore, analysing its effects when administered intranasally is essential to support potential clinical applications in humans. This study aims to determine the impact of intranasal GAL(1-15) on depressive-like behaviour using the FST and on alcohol-seeking using the alcohol self-administration in rats.
Intranasally, GAL(1-15) produced an inverted U-shaped dose-response curve 30 minutes after administration, with the 75 μg dose increasing immobility and reducing activity in the FST (p <0.001;according to ANOVA), an effect maintained with higher doses. One hour later, only 75 μg remained effective, reproducing a sustained depressive-like profile similar to that observed via ICV. In addition, after one hour of intranasal administration, GAL(1-15) 75 μg significantly reduced the number of reinforcements and active lever presses (p<0.01) in the alcohol self-administration test, according to Student t-test.
In conclusion, these findings deepen our understanding of intranasally GAL(1-15) and support its therapeutic potential in mood disorders in combination with SSRIs and AUDs, reinforcing its possible translation to human models.
Supported by:PID2020-114392RB-I00/AEI/10.13039/501100011033; PID2024-156923OB-I00, EXP2022/008766; 2025I009 and PPRO-B4-2024-010.