Predator odor (TMT) exposure potentiates interoceptive sensitivity to alcohol and increases GABAergic gene expression in the anterior insular cortex and nucleus accumbens in male rats

Tyler, Ryan E.; Bluitt, Maya N.; Voorhies, Kalynn Van; Ornelas, Laura C.; Weinberg, Benjamin Z S; Besheer, Joyce

doi:10.1016/j.alcohol.2022.07.002

Cited by 4 publications

(1 citation statement)

References 67 publications

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“…Using drug discrimination techniques, animals can be trained to discriminate the interoceptive effects of alcohol from vehicle (e.g., saline, water) using operant and Pavlovian drug discrimination techniques [7, 20–23, 29–38]. In the present study the functional role of mGlu 2 and mGlu 3 receptors in the interoceptive effects of alcohol (2.0 g/kg) were assessed using both operant and Pavlovian discrimination procedures.…”

Section: Introductionmentioning

confidence: 99%

mGlu₂and mGlu₃receptor negative allosteric modulators attenuate the interoceptive effects of alcohol in male and female rats

Tyler

Blough

Landavazo

et al. 2022

Preprint

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All drugs with the potential for addiction liability, including alcohol, produce distinct interoceptive stimulus effects that influence drug intake. Our lab has shown involvement of Group II metabotropic receptors (mGlu2/3) in the expression of alcohol interoceptive effects using a nonspecific mGlu2/3 agonist and antagonist. Furthermore, the anterior insular cortex (aIC) is a hub for interoceptive processing, including the interoceptive effects of alcohol. Therefore, the goal of the present work was to assess the independent functional contribution of mGlu2 and mGlu3, and the role of mGlu3 in the aIC, in the interoceptive effects of alcohol. As such, male, Long-Evans rats were trained to discriminate the stimulus effects of alcohol (2 g/kg, i.g.) from water (i.g.) using an operant, 2-lever drug discrimination procedure. To assess involvement of mGlu2 and mGlu3 in the discriminative stimulus effects of alcohol, rats were administered the mGlu2 negative allosteric modulator (NAM, VU6001966; 0, 3, 6 mg/kg, i.p.) and the mGlu3-NAM (VU6010572; 0, 3, 6, 12 mg/kg, i.p.) before alcohol (2 g/kg, i.g.). mGlu2-NAM (6 mg/kg) and mGlu3-NAM (12 mg/kg) decreased alcohol-appropriate lever responses without affecting response rate, reflecting diminished interoceptive alcohol sensitivity. mGlu3-NAM microinjection (3 ug) into the aIC before alcohol decreased response rate to such an extent that alcohol-appropriate lever responding could not be determined. As such, mGlu3-NAM was tested in the aIC before water administration to determine if VU6010572 substitutes for alcohol. mGlu3-NAM VU6010572 (3 ug) in the aIC produced partial alcohol-like stimulus effects without affecting response rate. These data indicate that the newly developed mGlu2 and mGlu3 NAMs can modulate interoceptive effects of alcohol. The opposing effects of systemic vs. microinjected (aIC) mGlu3-NAM on alcohol interoceptive effects may reflect differences in receptor binding, a functionally relevant metabolite, and/or brain region differences in receptor function.

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Section: Introductionmentioning

confidence: 99%

mGlu₂and mGlu₃receptor negative allosteric modulators attenuate the interoceptive effects of alcohol in male and female rats

Tyler

Blough

Landavazo

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

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Differential c-Fos Response in Neurocircuits Activated by Repeated Predator Stress in Male and Female C57BL/6J Mice with Stress Sensitive or Resilient Alcohol Intake Phenotypes

Clark,

Li,

Nipper

et al. 2023

Neuroscience

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Advances in translating mGlu2 and mGlu3 receptor selective allosteric modulators as breakthrough treatments for affective disorders and alcohol use disorder

Tyler

Besheer

Joffe

2022

Pharmacology Biochemistry and Behavior

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Predator odor (TMT) exposure potentiates interoceptive sensitivity to alcohol and increases GABAergic gene expression in the anterior insular cortex and nucleus accumbens in male rats

Cited by 4 publications

References 67 publications

mGlu₂and mGlu₃receptor negative allosteric modulators attenuate the interoceptive effects of alcohol in male and female rats

mGlu₂and mGlu₃receptor negative allosteric modulators attenuate the interoceptive effects of alcohol in male and female rats

Differential c-Fos Response in Neurocircuits Activated by Repeated Predator Stress in Male and Female C57BL/6J Mice with Stress Sensitive or Resilient Alcohol Intake Phenotypes

Advances in translating mGlu2 and mGlu3 receptor selective allosteric modulators as breakthrough treatments for affective disorders and alcohol use disorder

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Predator odor (TMT) exposure potentiates interoceptive sensitivity to alcohol and increases GABAergic gene expression in the anterior insular cortex and nucleus accumbens in male rats

Cited by 4 publications

References 67 publications

mGlu2and mGlu3receptor negative allosteric modulators attenuate the interoceptive effects of alcohol in male and female rats

mGlu2and mGlu3receptor negative allosteric modulators attenuate the interoceptive effects of alcohol in male and female rats

Differential c-Fos Response in Neurocircuits Activated by Repeated Predator Stress in Male and Female C57BL/6J Mice with Stress Sensitive or Resilient Alcohol Intake Phenotypes

Advances in translating mGlu2 and mGlu3 receptor selective allosteric modulators as breakthrough treatments for affective disorders and alcohol use disorder

Contact Info

Product

Resources

About

mGlu₂and mGlu₃receptor negative allosteric modulators attenuate the interoceptive effects of alcohol in male and female rats

mGlu₂and mGlu₃receptor negative allosteric modulators attenuate the interoceptive effects of alcohol in male and female rats