scholarly journals The Ethanol Metabolite Acetic Acid Activates Mouse Nucleus Accumbens Shell Medium Spiny Neurons

2021 ◽  
Author(s):  
Andrew D. Chapp ◽  
Paul G Mermelstein ◽  
Mark J Thomas
Keyword(s):  
Acetic Acid ◽  
Nucleus Accumbens ◽  
Neuronal Excitability ◽  
Ethanol Consumption ◽  
Synaptic Activity ◽  
Medium Spiny Neurons ◽  
Nucleus Accumbens Shell ◽  
Spiny Neurons ◽  
The Impact ◽  
Reward Circuit

While ethanol consumption leads to an array of neurophysiological alterations involving the neural circuits for reward, the underlying mechanisms remain unclear. Acetic acid is a major metabolite of ethanol with high bioactivity and potentially significant pharmacological importance in regulating brain function. Yet the impact of acetic acid on reward circuit function has not been well explored. Given the rewarding properties associated with ethanol consumption, we investigated the acute effects of ethanol and/or acetic acid on the neurophysiological function of medium spiny neurons of the nucleus accumbens shell, a key node in the mammalian reward circuit. We find that acetic acid, but not ethanol, provided a rapid and robust boost in neuronal excitability at physiologically relevant concentrations, while both compounds enhanced glutamatergic synaptic activity. These effects were consistent across both sexes in C57BL/6J mice. Overall, our data suggest acetic acid is a promising candidate mediator for ethanol effects on mood and motivation that deserves further investigation.

scholarly journals Prolonged Consumption of Sucrose in a Binge-Like Manner, Alters the Morphology of Medium Spiny Neurons in the Nucleus Accumbens Shell

2016 ◽  
Vol 10 ◽  
Author(s):  
Paul M. Klenowski ◽  
Masroor R. Shariff ◽  
Arnauld Belmer ◽  
Matthew J. Fogarty ◽  
Erica W. H. Mu ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Medium Spiny Neurons ◽  
Nucleus Accumbens Shell ◽  
Spiny Neurons

scholarly journals Ethanol Experience Enhances Glutamatergic Ventral Hippocampal Inputs to D1 Receptor-Expressing Medium Spiny Neurons in the Nucleus Accumbens Shell

2018 ◽  
Author(s):  
Daniel M. Kircher ◽  
Heather Aziz ◽  
Regina A. Mangieri ◽  
Richard A. Morrisett
Keyword(s):  
Nucleus Accumbens ◽  
Ampa Receptors ◽  
Critical Role ◽  
Alcohol Exposure ◽  
Ethanol Consumption ◽  
Ethanol Exposure ◽  
D1 Receptor ◽  
Medium Spiny Neurons ◽  
Spiny Neurons ◽  
Glutamatergic Signaling

ABSTRACTNucleus accumbens dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) have been implicated in the formation of dependence to many drugs of abuse including alcohol. Previous studies have revealed that acute alcohol exposure suppresses glutamatergic signaling within the accumbens and repeated alcohol exposure enhances glutamatergic signaling. D1-MSNs receive glutamatergic input from several brain regions and it is not currently known how individual inputs onto D1-MSNs are altered by alcohol experience. To Address this, we used virally mediated expression of Channelrhodopsin (ChR2) in ventral hippocampal (vHipp) glutamate neurons to selectively activate vHipp to D1-MSN synapses and compared synaptic adaptations in response to low and high alcohol experiencein vitroandin vivo. Alcohol experience enhanced glutamatergic activity and abolished long-term depression (LTD) at ventral hippocampal (vHipp) to D1-MSN synapses. Following chronic alcohol experience GluA2-lacking AMPA receptors, which are Ca-permeable, were inserted into vHipp to D1-MSN synapses. These alcohol-induced adaptations of glutamatergic signaling occurred at lower levels of exposure than previously reported. The loss of LTD expression and enhancement in glutamatergic signaling from the vHipp to D1-MSNs in the nucleus accumbens may play a critical role in the formation of alcohol dependence and enhancements in ethanol consumption. Reversal of alcohol-induced insertion of Ca-permeable AMPA receptors and enhancement of glutamatergic activity at vHipp to D1-MSNs presents potential targets for intervention during early exposure to alcohol.SIGNIFICANCE STATEMENTThe work presented here is the first to elucidate how an individual glutamatergic input onto D1-MSNs of the accumbens shell (shNAc) are altered by repeated ethanol exposure. Our findings suggest that glutamatergic input from the ventral hippocampus (vHipp) onto D1-MSNs is enhanced following drinking in a two-bottle choice (2BC) paradigm and is further enhanced by chronic intermittent ethanol (CIE) vapor exposure which escalated volitional ethanol intake. A critical finding was the insertion of Ca-permeable AMPA receptors into vHipp-shNAc D1-MSN synapses following CIE exposure, and more importantly following ethanol consumption in the absence of vapor exposure. These findings suggest that enhancements of glutamatergic input from the vHipp and insertion of Ca-permeable AMPARs play a role in the formation of ethanol dependence.

scholarly journals Morphine differentially alters the synaptic and intrinsic properties of D1R- and D2R-expressing medium spiny neurons in the nucleus accumbens

2019 ◽  
Author(s):  
Dillon S. McDevitt ◽  
Benjamin Jonik ◽  
Nicholas M. Graziane
Keyword(s):  
Nucleus Accumbens ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
D1 Receptor ◽  
Medium Spiny Neurons ◽  
Nucleus Accumbens Shell ◽  
Membrane Excitability ◽  
Action Potential Firing ◽  
Spiny Neurons ◽  
Functional Output

AbstractExposure to opioids reshapes future reward and motivated behaviors partially by altering the functional output of medium spiny neurons (MSNs) in the nucleus accumbens shell. Here, we investigated how morphine, a highly addictive opioid, alters synaptic transmission and intrinsic excitability on dopamine D1-receptor (D1R) expressing and dopamine D2-receptor (D2R) expressing MSNs, the two main output neurons in the nucleus accumbens shell. Using whole-cell electrophysiology recordings, we show, that 24 h abstinence following repeated non-contingent administration of morphine (10 mg/kg, i.p.) in mice reduces miniature excitatory postsynaptic current (mEPSC) frequency and miniature inhibitory postsynaptic current (mIPSC) frequency on D2R-MSNs, with concomitant increases in D2R-MSN intrinsic membrane excitability. We did not observe any changes on synaptic or intrinsic changes on D1R-MSNs. Lastly, in an attempt to determine the integrated effect of the synaptic and intrinsic alterations on the overall functional output of D2R-MSNs, we measured the input-output efficacy by measuring synaptically-driven action potential firing. We found that both D1R-MSN and D2R-MSN output was unchanged following morphine treatment.

Sign in / Sign up

Export Citation Format

Share Document