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Chemogenetic Inactivation of Orbitofrontal Cortex Decreases Cue-induced Reinstatement of Ethanol and Sucrose Seeking in Male and Female Wistar Rats.
Alcohol Clin Exp Res. 2020 Jul 06 [Online ahead of print]AC

Abstract

BACKGROUND

The orbitofrontal cortex (OFC) encodes internal representations of outcomes and subjective value to facilitate flexible reward seeking. OFC activation is associated with drug seeking in both human subjects and animal models. OFC plays a role in alcohol use, but studies in animal models have produced conflicting results with some showing decreased seeking after OFC inactivation but others showing increased seeking or no changes. In part, this may be due to the different measures of alcohol seeking used (e.g., homecage drinking vs. operant seeking).

METHODS

We characterized the impact of transient inactivation of OFC (primarily lateral and, to a lesser extent, ventral subregions) using inhibitory hM4Di designer receptors exclusively activated by designer drugs (DREADDs). OFC neurons were transiently inhibited during 10% and 20% alcohol (ethanol, EtOH) and sucrose homecage consumption, fixed ratio (FR1) operant self-administration, and cue-induced reinstatement of either 10% EtOH or sucrose in male and female rats.

RESULTS

OFC inactivation did not affect sucrose or EtOH consumption in the homecage, nor did it influence seeking or consumption under FR1 operant conditions. In contrast, OFC inactivation suppressed cued-induced reinstatement for both EtOH and sucrose in both male and female rats.

CONCLUSIONS

Our results are aligned with previous work indicating a selective suppressive effect of OFC inactivation on reinstatement for alcohol and other drugs of abuse. They extend these findings to demonstrate no effect on homecage consumption or FR1 seeking as well as showing an impact of sucrose reinstatement. These data indicate that OFC plays a uniquely important role when reward seeking is driven by associations between external stimuli and internal representations of reward value, both for natural and drug rewards. They further implicate the OFC as a key structure driving relapse-associated seeking and potentially contributing to alcohol use disorder and other diseases of compulsive reward seeking.

Authors+Show Affiliations

From the, Neuroscience and Behavior Graduate Program (JSH, DEM), University of Massachusetts Amherst, Amherst, Massachusetts, USA.Department of Psychological and Brain Sciences (ANB, TR, JDT, DEM), University of Massachusetts Amherst, Amherst, Massachusetts, USA.Department of Psychological and Brain Sciences (ANB, TR, JDT, DEM), University of Massachusetts Amherst, Amherst, Massachusetts, USA.Department of Psychological and Brain Sciences (ANB, TR, JDT, DEM), University of Massachusetts Amherst, Amherst, Massachusetts, USA.From the, Neuroscience and Behavior Graduate Program (JSH, DEM), University of Massachusetts Amherst, Amherst, Massachusetts, USA. Department of Psychological and Brain Sciences (ANB, TR, JDT, DEM), University of Massachusetts Amherst, Amherst, Massachusetts, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32628778

Citation

Hernandez, John S., et al. "Chemogenetic Inactivation of Orbitofrontal Cortex Decreases Cue-induced Reinstatement of Ethanol and Sucrose Seeking in Male and Female Wistar Rats." Alcoholism, Clinical and Experimental Research, 2020.
Hernandez JS, Binette AN, Rahman T, et al. Chemogenetic Inactivation of Orbitofrontal Cortex Decreases Cue-induced Reinstatement of Ethanol and Sucrose Seeking in Male and Female Wistar Rats. Alcohol Clin Exp Res. 2020.
Hernandez, J. S., Binette, A. N., Rahman, T., Tarantino, J. D., & Moorman, D. E. (2020). Chemogenetic Inactivation of Orbitofrontal Cortex Decreases Cue-induced Reinstatement of Ethanol and Sucrose Seeking in Male and Female Wistar Rats. Alcoholism, Clinical and Experimental Research. https://doi.org/10.1111/acer.14407
Hernandez JS, et al. Chemogenetic Inactivation of Orbitofrontal Cortex Decreases Cue-induced Reinstatement of Ethanol and Sucrose Seeking in Male and Female Wistar Rats. Alcohol Clin Exp Res. 2020 Jul 6; PubMed PMID: 32628778.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chemogenetic Inactivation of Orbitofrontal Cortex Decreases Cue-induced Reinstatement of Ethanol and Sucrose Seeking in Male and Female Wistar Rats. AU - Hernandez,John S, AU - Binette,Annalise N, AU - Rahman,Taryn, AU - Tarantino,Jeffrey D, AU - Moorman,David E, Y1 - 2020/07/06/ PY - 2020/03/21/received PY - 2020/06/24/accepted PY - 2020/7/7/pubmed PY - 2020/7/7/medline PY - 2020/7/7/entrez KW - Alcohol KW - DREADD KW - Prefrontal KW - Relapse KW - Sex Differences JF - Alcoholism, clinical and experimental research JO - Alcohol. Clin. Exp. Res. N2 - BACKGROUND: The orbitofrontal cortex (OFC) encodes internal representations of outcomes and subjective value to facilitate flexible reward seeking. OFC activation is associated with drug seeking in both human subjects and animal models. OFC plays a role in alcohol use, but studies in animal models have produced conflicting results with some showing decreased seeking after OFC inactivation but others showing increased seeking or no changes. In part, this may be due to the different measures of alcohol seeking used (e.g., homecage drinking vs. operant seeking). METHODS: We characterized the impact of transient inactivation of OFC (primarily lateral and, to a lesser extent, ventral subregions) using inhibitory hM4Di designer receptors exclusively activated by designer drugs (DREADDs). OFC neurons were transiently inhibited during 10% and 20% alcohol (ethanol, EtOH) and sucrose homecage consumption, fixed ratio (FR1) operant self-administration, and cue-induced reinstatement of either 10% EtOH or sucrose in male and female rats. RESULTS: OFC inactivation did not affect sucrose or EtOH consumption in the homecage, nor did it influence seeking or consumption under FR1 operant conditions. In contrast, OFC inactivation suppressed cued-induced reinstatement for both EtOH and sucrose in both male and female rats. CONCLUSIONS: Our results are aligned with previous work indicating a selective suppressive effect of OFC inactivation on reinstatement for alcohol and other drugs of abuse. They extend these findings to demonstrate no effect on homecage consumption or FR1 seeking as well as showing an impact of sucrose reinstatement. These data indicate that OFC plays a uniquely important role when reward seeking is driven by associations between external stimuli and internal representations of reward value, both for natural and drug rewards. They further implicate the OFC as a key structure driving relapse-associated seeking and potentially contributing to alcohol use disorder and other diseases of compulsive reward seeking. SN - 1530-0277 UR - https://www.unboundmedicine.com/medline/citation/32628778/Chemogenetic_Inactivation_of_Orbitofrontal_Cortex_Decreases_Cue-Induced_Reinstatement_of_Ethanol_and_Sucrose_Seeking_in_Male_and_Female_Wistar_Rats L2 - https://doi.org/10.1111/acer.14407 DB - PRIME DP - Unbound Medicine ER -
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