Melanin Concentrating Hormone

The expression pattern of melanin-concentrating hormone (MCH) neurons and receptors in the CNS support a potential role for MCH in a variety of physiological functions including stress, regulation of neuroendocrine processes, and feeding. Of these functions, MCH effects on feeding behavior and energy homeostasis have been most studied,156 but MCHR1 antagonists may be a novel approach to the treatment of anxiety. MCH cell bodies are located in the lateral hypothalamus and zona incerta with widespread projections to limbic structures such as hippocampus, septum, amygdala, locus coeruleus, dorsal raphe nucleus, and the shell of the nucleus accumbens, areas that are involved in the regulation of emotion.157 The MCHR1 nonpeptide antagonists ATC-0065 and ATC-0175 (Figure 12c) reverse swim stress-induced anxiety in the EPM in rats and decrease temperature change in the stress-induced hyperthermia model in mice.158 ATC-0175 also increased social interaction between unfamiliar rats and decreased distress vocalizations in guinea pig pups. The compounds had no effect on marble burying in mice, a model of OCD. The MCHR1 antagonist SNAP-7941 (Figure 12c) decreased distress vocalizations in guinea pig pups and increased social interaction time compared with vehicle in rats.159

While the few small molecule antagonists that have been tested seem to produce anxiolytic effects in animal models, studies using the endogenous peptide agonist MCH have produced mixed results. Consistent with the antagonist results, MCH injected bilaterally into the medial preoptic area decreases the amount of time rats spend in the open arms of the elevated plus maze.151 In contrast, when MCH is injected into the cerebral ventricles, it increases licking in the rat Vogel conflict test160 and increases time spent in the open arms of the elevated plus maze161 supporting an anxiogenic effect. It is unclear why MCH seems to produce opposite effects in some cases.

Conquering Fear In The 21th Century

Conquering Fear In The 21th Century

The Ultimate Guide To Overcoming Fear And Getting Breakthroughs. Fear is without doubt among the strongest and most influential emotional responses we have, and it may act as both a protective and destructive force depending upon the situation.

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