Anxiolytic Effects of the MCH1R Antagonist TPI 1361-17

Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that acts on the MCH1 receptor. MCH1R is expressed widely throughout the brain, particularly in regions thought to be involved in the regulation of stress and emotional response. The role of MCH in anxiety has been controversial, however. Central administration of MCH has been reported to promote or reduce anxiety-like behaviors. The anxiolytic activity of several MCH1R antagonists has also been debated. To address this issue, we have tested whether TPI 1361-17, a highly specific and high affinity MCH1R antagonist, exerts anxiolytic effects in two commonly used models of anxiety, the elevated plus maze and the light–dark transition test. We show that this MCH1R antagonist exerts potent anxiolytic effects in both assays. Our study therefore supports previous studies indicating that MCH1R antagonists may be useful in the treatment of anxiety.