Ethanol has concentration-dependent effects on hypothalamic POMC neuronal excitability

Jonna M. Leyrer-Jackson, Erin K. Nagy, Lauren E. Hood, Jason M. Newbern, Cassandra D. Gipson, M. Foster Olive

Research output: Contribution to journalArticle

Abstract

Alcohol abuse is a worldwide public health concern, yet the precise molecular targets of alcohol in the brain are still not fully understood. Alcohol may promote its euphoric and motivational effects, in part, by activating the endogenous opioid system. One particular component of this system consists of pro-opiomelanocortin (POMC) -producing neurons in the arcuate nucleus (ArcN) of the hypothalamus, which project to reward-related brain areas. To identify the physiological effects of ethanol on ArcN POMC neurons, we utilized whole cell patch-clamp recordings and bath application of ethanol (5–40 mM) to identify alterations in spontaneous baseline activity, rheobase, spiking characteristics, or intrinsic neuronal properties. We found that 10 mM ethanol increased the number of depolarization-induced spikes in the majority of recorded cells, whereas higher concentrations of ethanol (20–40 mM) decreased the number of spikes. Interestingly, we found that basal firing rates of ArcN POMC neurons may predict physiological responding to ethanol. Rheobase and spontaneous activity, measured by spontaneous excitatory post-synaptic potentials (EPSPs) at rest, were unchanged after exposure to ethanol, regardless of concentration. These results suggest that ethanol has concentration-dependent modulatory effects on ArcN POMC neuronal activity, which may be relevant to treatments for alcohol use disorders that target endogenous opioid systems.

Original languageEnglish (US)
Pages (from-to)103-112
Number of pages10
JournalAlcohol
Volume86
DOIs
StatePublished - Aug 2020

Keywords

  • Alcohol
  • Hypothalamus
  • Neuronal excitability
  • POMC
  • Pro-opiomelanocortin
  • Rheobase

ASJC Scopus subject areas

  • Health(social science)
  • Biochemistry
  • Toxicology
  • Neurology
  • Behavioral Neuroscience

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  • Cite this

    Leyrer-Jackson, J. M., Nagy, E. K., Hood, L. E., Newbern, J. M., Gipson, C. D., & Olive, M. F. (2020). Ethanol has concentration-dependent effects on hypothalamic POMC neuronal excitability. Alcohol, 86, 103-112. https://doi.org/10.1016/j.alcohol.2020.04.001