• Ronald McGregor, Alessandra Matzeu, Thomas C Thannickal, Frank Wu, Marcia Cornford, Rémi Martin-Fardon, and Jerome M Siegel.
• Neuropsychiatric Institute and Brain Research Institute, University of California, Los Angeles, 90095, USA; Neurobiology Research, VA Greater Los Angeles Healthcare System, North Hills, Los Angele, California 91343, USA. Electronic address: icelos3@gmail.com.
• Neuroscience. 2023 Jul 1; 522: 1101-10.

AbstractHuman heroin addicts and mice administered morphine for a 2 week period show a greatly increased number of hypothalamic hypocretin (Hcrt or orexin) producing neurons with a concomitant reduction in Hcrt cell size. Male rats addicted to cocaine similarly show an increased number of detectable Hcrt neurons. These findings led us to hypothesize that humans with alcohol use disorder (AUD) would show similar changes. We now report that humans with AUD have a decreased number and size of detectable Hcrt neurons. In addition, the intermingled melanin concentrating hormone (MCH) neurons are reduced in size. We saw no change in the size and number of tuberomammillary histamine neurons in AUD. Within the Hcrt/MCH neuronal field we found that microglia cell size was increased in AUD brains. In contrast, male rats with 2 week alcohol exposure, sufficient to elicit withdrawal symptoms, show no change in the number or size of Hcrt, MCH and histamine neurons, and no change in the size of microglia. The present study indicates major differences between the response of Hcrt neurons to opioids and that to alcohol in human subjects with a history of substance abuse.Published by Elsevier Ltd.

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