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14-03-2013 | Pharmacology | Article

Neuropeptides are potential psychotherapeutic target


Free abstract

medwireNews: Scientists have identified a role for two neuropeptides, hypocretin-1 and melanin-concentrating hormone (MCH), in regulating human mood and alertness.

The findings could pave the way for new treatments for depression and other psychiatric disorders, say the researchers writing in Nature Communications.

Jerome Siegel (University of California at Los Angeles, USA) and team used microdialysis to monitor levels of the two hormones in the amygdala of eight patients with seizures but no known psychiatric illness.

The patients were implanted bilaterally with electrodes and neurohormones were sampled using microdialysis 2-5 days later. Hypocretin and MCH levels were measured while the patients performed a range of activities, such as watching television, interacting socially, eating, and sleeping, and while experiencing pain.

Siegel's team found that levels of both hormones fluctuated with the patients' emotional state.

For instance, hypocretin-1 levels were highest during positive emotion, social interaction, and anger. Interestingly, these behaviors are known to induce cataplexy in people who suffer from narcolepsy, they remark.

Also, hypocretin-1 levels were higher during waking periods with positive emotions than in waking periods with negative emotions.

Meanwhile, MCH levels were lowest during social interaction but increased after eating. There was also a dissociation between MCH and hypocretin-1 during the sleep-wake cycle, whereby MCH levels increased at the onset of sleep and hypocretin-1 levels increased at the onset of wakening.

Both peptides were at minimal levels during periods of postoperative pain, despite high levels of arousal.

Taken together, the findings indicate that levels of the two peptides "are not simply linked to arousal, but rather to specific emotions and state transitions," write Siegel and co-authors.

Thus, abnormalities in the pattern of activation of these systems may contribute to a number of psychiatric disorders, including depression and narcolepsy, and targeting the peptides with drugs or other means could have therapeutic value.

The authors note that hypocretin antagonists are already in development for use as sleeping pills; the current findings suggest that these drugs will alter mood as well as sleep tendency.

By Joanna Lyford, Senior medwireNews Reporter

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