ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2022
Characterization of DREADD receptor expression and function in rhesus macaques trained to discriminate ethanol.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 9 citations in OpenAlex.
- Nucleus accumbens core chemogenetic excitation in male mice and chemogenetic inhibition in female mice reduced ethanol reward.Biology of sex differences · 2025Article
- Evolutionarily conserved neural responses to affective touch in monkeys transcend consciousness and change with age.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Imaging-based chemogenetics for dissecting neural circuits in nonhuman primates.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2024Review
- The use of chemogenetic actuator ligands in nonhuman primate DREADDs-fMRI.Current research in neurobiology · 2023Article
- 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.Alcohol (Fayetteville, N.Y.) · 2022Article
- Applications of chemogenetics in non-human primates.Current opinion in pharmacology · 2022Review
- Impact of putamen inhibition by DREADDs on schedule-induced drinking in rhesus monkeys.Journal of the experimental analysis of behavior · 2022Article
- Dissecting the Prefrontal Network With Pathway-Selective Manipulation in the Macaque Brain-A Review.Frontiers in neuroscience · 2022Review
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Authors and funding
6 authors at 1 institution in 1 country.
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Abstract
Circuit manipulation has been a staple technique in neuroscience to identify how the brain functions to control complex behaviors. Chemogenetics, including designer receptors exclusively activated by designer drugs (DREADDs), have proven to be a powerful tool for the reversible modulation of discrete brain circuitry without the need for implantable devices, thereby making them especially useful in awake and unrestrained animals. This study used a DREADD approach to query the role of the nucleus accumbens (NAc) in mediating the interoceptive effects of 1.0 g/kg ethanol (i.g.) in rhesus monkeys (n = 7) using a drug discrimination procedure. After training, stereotaxic surgery was performed to introduce an AAV carrying the human muscarinic 4 receptor DREADD (hM4Di) bilaterally into the NAc. The hypothesis was that decreasing the output of the NAc by activation of hM4Di with the DREADD actuator, clozapine-n-oxide (CNO), would potentiate the discriminative stimulus effect of ethanol (i.e., a leftward shift the ethanol dose discrimination curve). The results showed individual variability shifts of the ethanol dose-response determination under DREADD activation. Characterization of the expression and function of hM4Di with MRI, immunohistochemical, and electrophysiological techniques found the selectivity of NAc transduction was proportional to behavioral effect. Specifically, the proportion of hM4Di expression restricted to the NAc was associated with the potency of the discriminative stimulus effects of ethanol. Together, these experiments highlight the NAc in mediating the interoceptive effects of ethanol, provide a framework for validation of chemogenetic tools in primates, and underscore the importance of robust within-subjects examination of DREADD expression for interpretation of behavioral findings.
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