Galanin (1-15) enhancement of the behavioral effects of a 5-HT1AR agonist and fluoxetine in the forced swimming test gives a new therapeutic strategy against depression: possible role of GALR1-GALR2-5-HT1AR heteroreceptor complexes

Abstract

Major Depression is the most frequent mood disorder, with a lifetime prevalence that has been reported to range from 7% to 21%. It is associated with a substantial functional impairment, diminished quality of life, increased burden both for patients and caregivers, as well as with a higher risk of mortality. Although the underlying mechanisms have not yet been clearly defined in the last decade the importance of the role of neuropeptides, including Galanin (GAL) and the N-terminal fragment GAL(1-15) and/or their receptors in the treatment of stress-related mood disorders is becoming increasingly apparent. We have described that GAL(1-15) induces strong depression-related and anxiogenic-like effects in rats and these effects were significantly stronger than the ones induced by GAL. The GALR1-GALR2 heteroreceptor complexes in the dorsal hippocampus and dorsal raphe (DR) were involved in these effects and demonstrated also in cellular models. Although several neurotransmitter systems and brain areas have been implicated in depression, the pharmacological treatment of major depression is mainly based on drugs elevating serotonergic (5-HT) activity. Specifically, selective 5-HT reuptake inhibitors (SRRIs) are the most commonly used for treatment of major depression. In particular, Fluoxetine (FLX) is usually chosen for the treatment of symptoms of depression In view of these results the purpose of the current study was to assess the ability of GAL(1–15) to modulate the behavioral effects of the 5-HT1AR agonist 8-OH-DPAT and FLX.

We have analyzed the effect of GAL (1–15) on the 5-HT1AR agonist 8-OH-DPAT and FLX-mediated responses in a behavioral test of depression.