Galanin (1-15) Enhances the Behavioral Effects of Fluoxetine in the Olfactory Bulbectomy Rat, Suggesting a New Augmentation Strategy in Depression

Abstract

Background Selective serotonergic reuptake inhibitors, including fluoxetine (FLX), are the most commonly used for the treatment of major depression. However, they are only effective for remission in 30% of patients. Recently we observed that Galanin (1-15) [GAL(1-15)] enhanced the antidepressant effects of FLX in naïve animals suggesting a new augmentation strategy in depression. Methods We have analyzed in an animal model of depression, the olfactory bulbectomy (OBX) rats the effect of GAL(1–15) on FLX-mediated responses in the forced swimming test (FST) and in sucrose preference test (SPT) and the involvement of GALR2 with its antagonist M871. We have also studied the corticosterone levels in OBX after the coadministration of GAL(1-15) with FLX. Moreover, we studied whether the effects of GAL(1–15) on FLX actions were mediated via 5-HT1AR analyzing the binding characteristics, mRNA levels and the functionality of 5-HT1AR in the dorsal hippocampus. Results GAL(1-15) enhances the antidepressant-like effects induced by FLX in OBX animals in the FST and in the SPT. The involvement of the GALR2 was demonstrated with M871. Importantly, the mechanism underlying the GAL(1-15)/FLX interactions in the OBX animals involves the 5-HT1AR in the hippocampus at the plasma membrane (increase of affinity and density of 5HT1AR in the DG) and transcriptional (increase of 5HT1AR mRNA levels in DG and CA1) levels. Besides, the coadministration of GAL(1-15) and FLX also reduced OBX-increased corticosterone levels Conclusions The results open up the possibility to use GAL(1-15) in combination with FLX as a novel strategy for the treatment of depression.

The Combination of Galanin (1–15) and Escitalopram in Rats Suggests a New Strategy for Alcohol Use Disorder Comorbidity with Depression

“…The interaction between GAL(1–15) and the 5HT1A receptor has been described both at the functional level and at the receptor level in recent years [ 22 , 26 , 27 , 28 , 61 ]. The existence of a 5HT1A-GALR1-GALR2 receptor mosaic would explain these results [ 26 , 62 , 63 , 64 ].…”

Mind, Mood and Microbiota—Gut–Brain Axis in Psychiatric Disorders

“…Furthermore, a study conducted by Flores-Burgess et al introduces the potential of utilizing a combination of galanin (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) and fluoxetine as an innovative approach for treating depression. This suggests the presence of underlying immune and neuroregulatory mechanisms that may mediate the impact of stress on the gastrointestinal tract [24]. Cortisol exerts its influence within the central nervous system (CNS) through both hormonal and neural communication pathways.…”