Biological Psychiatry: Rapid Eye Movement Sleep Engages Melanin-Concentrating Hormone Neurons to Reduce Cocaine Seeking

Substance use relapse is a major barrier in treating substance use disorders. Withdrawal from substance use often causes sleep disruptions, which can aggravate withdrawal symptoms and increase the likelihood of relapse. A group of investigators, including Pitt Psychiatry scientists Rong Guo, PhD (Scientist, Allen Institute; former Pitt Psychiatry postdoctoral scholar), Yao Wang, PhD (Research Assistant Professor of Psychiatry), and Yanhua Huang, PhD (Pittsburgh Foundation Endowed Professor in Brain and Behavior Research and Associate Professor of Psychiatry), examined the correlations between the intensity of cocaine seeking and key sleep features. They published the results in Biological Psychiatry. 

The investigators trained male rats to self-administer cocaine. After long-term withdrawal, the scientists tested for causal relationships using behavioral, chemogenetic, or optogenetic methods to selectively increase rapid eye movement (REM) sleep. They then measured behavioral and electrophysiological outcomes to probe for cellular and circuit mechanisms underlying REM sleep-mediated regulation of cocaine seeking. 

Findings from the study showed that a selective set of REM sleep features were preferentially associated with the intensity of cue-induced cocaine seeking after drug withdrawal. The investigators also found that selectively increasing REM sleep time and continuity by environmental warming attenuated a withdrawal time-dependent intensification of cocaine seeking, suggesting that REM sleep may increase the likelihood of withdrawal and vulnerability to relapse. In addition, warming increased the activity of lateral hypothalamic melanin-concentrating hormone (MCH) neurons during prolonged REM sleep episodes and counteracted cocaine-induced synaptic accumulation of calcium-permeable AMPA receptors in the nucleus accumbens, indicating that MCH neuron activities can be selectively targeted during REM sleep to reduce substance use relapse. 

“These results highlight REM sleep and, in particular, MCH neuron activities in REM sleep, in regulating drug relapse, and provide an important rationale for therapeutic development in the future.” said Dr. Huang, the study’s senior author.

Rapid eye movement sleep engages melanin-concentrating hormone neurons to reduce cocaine seeking
Guo R, Wang Y, Yan R, Chen B, Ding W, Gorczyca MT, Ozsoy S, Cai L, Hines RL, Tseng GC, Allocca G, Dong Y, Fang J, Huang YH
Biological Psychiatry, June 13, 2022, https://doi.org/10.1016/j.biopsych.2022.06.006