Research on substance use disorders has largely focused on understanding the key neural circuits and neurotransmitter systems that are altered, and on behavioral and pharmacological interventions. However, emerging research findings suggest that alcohol use disorder (AUD) is associated with alterations in energy metabolism and can accelerate brain aging. In this episode I talk with Dr. Corinde Wiers about substance use disorders with a focus on her recent clinical trials which show that ketone (b-hydroxybutyrate) supplementation can reduce craving for alcohol in people with AUD and can reduce alcohol withdrawal symptoms. We discuss the potential mechanisms that may explain the efficacy of ketone supplementation – and interventions that elevate endogenous ketone production (fasting, exercise, and ketogenic diets) – in AUD. Whether or not ketogenic interventions are beneficial for individuals with other addictions (opioids, cocaine, nicotine, gambling..) remains to be determined.

LINKS:

Dr. Wiers webpage at the University of Pennsylvania: https://www.med.upenn.edu/apps/faculty/index.php/g332/p9389303

Dr. Wiers’ publications discussed in this podcast:

https://pmc.ncbi.nlm.nih.gov/articles/PMC8034849/pdf/abf6780.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC8670944/pdf/fpsyt-12-781668.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC10901540/pdf/pyae009.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC10895037/pdf/fnut-11-1254341.pdf

Appetite (hunger and satiety) is controlled by neural circuits in the brain – particularly in the hypothalamus – and their reciprocal connections to peripheral organs involved in energy metabolism (gut and liver). Understanding the structural organization of these circuits (their synaptic connections) and their neurochemistry (particularly which neurotransmitters are used at which synapses) is of fundamental importance for human health and developing new treatments for metabolic disorders such as obesity and diabetes. Neuroscientist Henning Fenselau at the Max Planck Institute and University of Cologne Germany has made several major discoveries about how food intake and energy metabolism are regulated and the consequences of abnormalities in the underlying neural circuits. Among his recent findings concern how GLP-1 in the gut communicates with the brain via the vagus nerve, and the roles of specific synaptic signals (NPY, opioids, TRH, and GABA).

LINKS

Fenselau laboratory page: https://www.sf.mpg.de/research/fenselau

GLP-1, the vagus nerve, hunger, and sugar metabolism:

https://www.cell.com/action/showPdf?pii=S1550-4131%2821%2900219-9

Synaptic amplifier of hunger:

https://pmc.ncbi.nlm.nih.gov/articles/PMC10160008/pdf/nihms-1882224.pdf

Opioids and sugar appetite

https://www-science-org.proxy1.library.jhu.edu/doi/epdf/10.1126/science.adp1510

Brainstem – amygdala circuit during fasting

https://pmc.ncbi.nlm.nih.gov/articles/PMC11211344/pdf/41467_2024_Article_49766.pdf

One of the most remarkable feats of biological ‘wizardry’ in the animal kingdom is the ability of some cephalopods (octopuses, squids, and cuttlefish) to rapidly change the color, patterning, and texture of their skin so as to blend in with their background. They accomplish these feats through the linking of neural circuits in the visual system and brain to muscle cells that control the dispersion of pigment in specialized skin cells called chromatophores. But the details of the neural circuitry and the computational processes that control the camouflaging process remain largely unknown. In this episode Columbia University neuroscientist Tessa Montague talks about her research on the neurobiology of camouflage and the many challenges that must be overcome to better understand this remarkable phenomenon.

LINKS

Dr. Montague’s cuttlefish lab webpage: Tessamontague.com

Links to camouflaging cephalopods

https://www.youtube.com/watch?v=XocHDvHlcJM

https://www.youtube.com/watch?v=Ojb1pxcSr5E

Articles on the neurobiology of camouflage

https://www.cell.com/action/showPdf?pii=S0960-9822%2823%2901182-X

https://www.sciencedirect.com/science/article/pii/S0959438824000382?via%3Dihub

https://www.cell.com/action/showPdf?pii=S0960-9822%2823%2900757-1