It seems like this neuropeptide may play a key role in anhedonia
"Neurochemistry of the Transmission in the Central Nervous System", co-directed by Professor Zaida Díaz-Cabiale, has evidenced that a fragment of the "Galanin" neuropeptide -an endogenous molecule of the brain- is involved in anhedonia, which is the loss of the capacity to feel pleasure in daily activities, for instance, meals, social activity or sex, and, thus, one of the main symptoms in depressed patients.
These researchers have demonstrated for the first time the role of "GAL (1-15)" in the brain reward system of an animal model.
"We have verified through different experiments how animals modify their response to high-reinforcement appetitive stimuli, such as saccharine or sexual attraction, after the administration of the Galanin fragment", explains researcher Carmelo Millón, one of the authors of this study, published in Journal of Psychopharmacology.
Furthermore, in this article, in which a researcher of Karolinska Institute (Sweden) has participated, they have analyzed the brain reinforcement system at a molecular level, the circuit in charge of reinforcing positive behavior for individuals and species, and reaffirmed that the Galanin fragment acts directly on this neurological mechanism, reducing the circuit activity.
According to Millón, describing this fragment is essential to modulate the brain reward circuit, having interesting applications that go beyond treatments for depression, such as its possible use in drug-related addictions. "The understanding of these mechanisms opens the way for endless therapeutic strategies, hence its importance", he says.
Here is the full article
https://www.ncbi.nlm...pubmed/31081442
There isn't a great deal of available research and I have too much avolition to look for more, but this is very interesting.
https://www.ncbi.nlm.../pubmed/9928183
As is this
https://www.ncbi.nlm...les/PMC3759228/
"Thus, decreased mRNA for both TH and GAL mRNA in VTA resulting from AD treatment suggests that AD treatment may have decreased VTA-DA activity, perhaps by increasing extracellular GAL in VTA or by some other mechanism.
Studies of galanin receptor knockout mice indicate a role for both the galanin receptor type 1 (GalR1) and GalR2 in mouse models of anxiety. We have previously demonstrated that levels of galanin mRNA are increased in limbic brain nuclei after different modalities of antidepressant treatment in rats, whereas the behavioral effects of a subchronic selective serotonin reuptake inhibitor can be reversed by the galanin receptor antagonist M40. "
Could this be one of the missing pieces in the anhedonia puzzle? It seems very relevant for medication induced anhedonia too.
The pharmacological treatment of major depression is mainly based on drugs elevating serotonergic (5-HT) activity. Specifically, selective 5-HT reuptake inhibitors, including Fluoxetine (FLX), are the most commonly used for treatment of major depression. However, the understanding of the mechanism of action of FLX beyond its effect of elevating 5-HT is limited. The interaction between serotoninergic system and neuropeptides signaling could be a key aspect. We examined the ability of the neuropeptide Galanin(1-15) [GAL(1-15)] to modulate the behavioral effects of FLX in the forced swimming test (FST) and studied feasible molecular mechanisms. The data show that GAL(1-15) enhances the antidepressant-like effects induced by FLX in the FST, and we demonstrate the involvement of GALR1/GALR2 heteroreceptor complex in the GAL(1-15)-mediated effect using in vivo rat models for siRNA GALR1 or GALR2 knockdown. Importantly, 5-HT1A receptors (5HT1A-R) also participate in the GAL(1-15)/FLX interactions since the 5HT1AR antagonist WAY100635 blocked the behavioral effects in the FST induced by the coadministration of GAL(1-15) and FLX. The mechanism underlying GAL(1-15)/FLX interactions affected the binding characteristics as well as the mRNA levels of 5-HT1A-R specifically in the dorsal hippocampus while leaving unaffected mRNA levels and affinity and binding sites of this receptor in the dorsal raphe. The results open up the possibility to use GAL(1-15) as for a combination therapy with FLX as a novel strategy for treatment of depression.
https://www.ncbi.nlm...y-SvCWpfeumtI48
This article is saying that GAL1-15 fragment, the same compound listed above as a major cause of anhedonia, increased the "antidepressant" effects of fluoxetine.
Galanin also plays a major role in neurogenesis, for which SSRI'S effects are heavily attributed. I think this neuropeptide could play a major role in anhedonia,both depression and medication induced. What do you all think?
