ArticleFrontiers in behavioral neuroscience2018
Behavioral Effects of Acute Systemic Low-Dose Clozapine in Wild-Type Rats: Implications for the Use of DREADDs in Behavioral Neuroscience.
Article in Frontiers in behavioral neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 76 citations in OpenAlex.
- Behavioral impact of chemogenetic manipulations of 5-HT DRN neurons in transgenic Tph2-iCre rats.Psychopharmacology · 2026Article
- Clozapine Mitigates Lipopolysaccharide-Induced Cognitive Dysfunction by Modulating Cholinergic Function, Oxidative Stress, and Apoptotic Signaling in Rats.Life (Basel, Switzerland) · 2026Article
- Thermally induced neuronal plasticity in the hypothalamus mediates heat tolerance.Nature neuroscience · 2025Article
- Optogenetics and chemogenetics: key tools for modulating neural circuits in rodent models of depression.Frontiers in neural circuits · 2025Review
- Gene therapy for chronic pain management.Cell reports. Medicine · 2024Review
- Cingulate to septal circuitry facilitates the preference to affiliate with large peer groups.Current biology : CB · 2024Article
- Chemogenetic Excitation of Ventromedial Hypothalamic Steroidogenic Factor 1 (SF1) Neurons Increases Muscle Thermogenesis in Mice.Biomolecules · 2024Article
- Designer Receptor Exclusively Activated by Designer Drug (DREADD)-Mediated Activation of the Periaqueductal Gray Restores Nociceptive Descending Inhibition After Traumatic Brain Injury in Rats.Journal of neurotrauma · 2024Article
- Chemogenetic approaches reveal dual functions of microglia in seizures.Brain, behavior, and immunity · 2024Article
- Clozapine N-oxide, compound 21, and JHU37160 do not influence effortful reward-seeking behavior in mice.Psychopharmacology · 2024Article
- State-dependent memory retrieval: insights from neural dynamics and behavioral perspectives.Learning & memory (Cold Spring Harbor, N.Y.) · 2023Article
- Prefrontal cortex astroglia modulate anhedonia-like behavior.Molecular psychiatry · 2023Article
- 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
- A head-to-head comparison of two DREADD agonists for suppressing operant behavior in rats via VTA dopamine neuron inhibition.Psychopharmacology · 2023Article
- Prefrontal Cortex Astroglia Modulate Anhedonia-like Behavior.Research square · 2023Article
- Chemogenetic modulation of the medial prefrontal cortex regulates resistance to acute stress-induced cognitive impairments.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- A head-to-head comparison of two DREADD agonists for suppressing operant behavior in rats via VTA dopamine neuron inhibition.bioRxiv : the preprint server for biology · 2023Article
- Article
- The use of chemogenetic actuator ligands in nonhuman primate DREADDs-fMRI.Current research in neurobiology · 2023Article
- Characterization of Ultrapotent Chemogenetic Ligands for Research Applications in Nonhuman Primates.ACS chemical neuroscience · 2022Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Designer receptors exclusively activated by designer drugs (DREADDs) are popular tools used to manipulate the activity of defined groups of neurons. Recent work has shown that DREADD effects in the brain are most likely not mediated by the proposed ligand clozapine-N-oxide (CNO) but its metabolite clozapine (CLOZ). However, it is not known whether low doses of CLOZ required to activate DREADDs already have DREADD-independent effects on behavior as described for higher CLOZ doses used in previous preclinical studies. To close this gap, we compared effects of acute systemic (i.p.) CLOZ treatment vs. vehicle (VEH) in a wide range of behavioral tests in male wild-type rats. We found that CLOZ doses as low as 0.05-0.1 mg/kg significantly affected locomotion, anxiety and cognitive flexibility but had no effect on working memory or social interaction. These results highlight the need for careful controls in future chemogenetic experiments and show that previous results in studies lacking CNO/CLOZ controls may require critical re-evaluation.
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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 OpenQuestion graph.