ArticlePsychopharmacology2023
A head-to-head comparison of two DREADD agonists for suppressing operant behavior in rats via VTA dopamine neuron inhibition.
Article in Psychopharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Interrogating roles for VTA dopamine neurons in locomotion and ultrasonic vocalizations elicited by different classes of rewarding drugs.Psychopharmacology · 2026Article
- Ventral pallidum GABA neuron inhibition augments context-appropriate defensive responses to learned threat cues.Neurobiology of stress · 2026Article
- Chemogenetic Inhibition and Optogenetic Depotentiation of the Prelimbic Cortex to Paraventricular Thalamus Pathway Attenuate Abstinence-Induced Plasticity and Heroin Seeking in Rats.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
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- Prelimbic cortex is involved in the regulation of morphine-induced conditioned place preference in both resistant and sensitive mice.Scientific reports · 2025Article
- Adolescent THC impacts on mPFC dopamine-mediated cognitive processes in male and female rats.Psychopharmacology · 2025Article
- Cortico-striatal action control inherent of opponent cognitive-motivational styles.bioRxiv : the preprint server for biology · 2024Article
- Adolescent THC impacts on mPFC dopamine-mediated cognitive processes in male and female rats.bioRxiv : the preprint server for biology · 2024Article
- Comparison of three DREADD agonists acting on Gq-DREADDs in the ventral tegmental area to alter locomotor activity in tyrosine hydroxylase:Cre male and female rats.Behavioural brain research · 2023Article
- High dose administration of DREADD agonist JHU37160 produces increases in anxiety-like behavior in male rats.Behavioural brain research · 2023Article
- Chemogenetic activation of the ventral subiculum-BNST pathway reduces context fear expression.Learning & memory (Cold Spring Harbor, N.Y.) · 2023Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
rationaleDesigner receptors exclusively activated by designer drugs (DREADDs) are a tool for "remote control" of defined neuronal populations during behavior. These receptors are inert unless bound by an experimenter-administered designer drug, commonly clozapine-n-oxide (CNO). However, questions have emerged about the suitability of CNO as a systemically administered DREADD agonist.
objectivesSecond-generation agonists such as JHU37160 (J60) have been developed, which may have more favorable properties than CNO. Here we sought to directly compare effects of CNO (0, 1, 5, & 10 mg/kg, i.p.) and J60 (0, 0.03, 0.3, & 3 mg/kg, i.p.) on operant food pursuit.
methodsMale and female TH:Cre + rats and their wildtype (WT) littermates received cre-dependent hM4Di-mCherry vector injections into ventral tegmental area (VTA), causing inhibitory DREADD expression in VTA dopamine neurons of TH:Cre + rats. All rats were trained to stably lever press for palatable food on a fixed ratio 10 schedule, and doses of both agonists were tested on separate days in counterbalanced order.
resultsAll three CNO doses reduced operant rewards earned in rats with DREADDs, and no CNO dose had behavioral effects in WT controls. The highest J60 dose tested significantly reduced responding in DREADD rats, but this dose also increased responding in WTs, indicating non-specific effects. The magnitude of CNO and J60 effects in TH:Cre + rats were correlated and were present in both sexes.
conclusionsFindings demonstrate the usefulness of directly comparing DREADD agonists when optimizing behavioral chemogenetics, and highlight the importance of proper controls, regardless of the DREADD agonist employed.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.