TY - JOUR
T1 - Ethanol has concentration-dependent effects on hypothalamic POMC neuronal excitability
AU - Leyrer-Jackson, Jonna M.
AU - Nagy, Erin K.
AU - Hood, Lauren E.
AU - Newbern, Jason M.
AU - Gipson, Cassandra D.
AU - Olive, M. Foster
N1 - Funding Information:
This work was supported by Public Health Service grants F32AA027962 to JMLJ, AA025590 to MFO, and DA044479 , DA045881 , DA036569 , and DA046526 to CDG.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/8
Y1 - 2020/8
N2 - 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.
AB - 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.
KW - Alcohol
KW - Hypothalamus
KW - Neuronal excitability
KW - POMC
KW - Pro-opiomelanocortin
KW - Rheobase
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U2 - 10.1016/j.alcohol.2020.04.001
DO - 10.1016/j.alcohol.2020.04.001
M3 - Article
C2 - 32304714
AN - SCOPUS:85084967449
SN - 0741-8329
VL - 86
SP - 103
EP - 112
JO - Alcohol
JF - Alcohol
ER -