ArticlePsychopharmacology2023
Repeated chemogenetic activation of dopaminergic neurons induces reversible changes in baseline and amphetamine-induced behaviors.
Article in Psychopharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 6 citations in OpenAlex.
- Differential effects of acute versus repeated chemogenetic activation of the mesocorticolimbic dopamine pathway on cocaine choice in male and female TH:Cre rats.ASPET discovery · 2026Article
- Optogenetic stimulation of midbrain dopaminergic neurons rescues hippocampal synaptic plasticity deficits in a mouse model of Alzheimer's disease.Translational psychiatry · 2025Article
- Adolescent chemogenetic activation of dopaminergic neurons leads to reversible decreases in amphetamine-induced stereotypic behavior.Molecular brain · 2024Article
- Interactions between Lateral Hypothalamic Orexin and Dorsal Raphe Circuitry in Energy Balance.Brain sciences · 2024Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
rationaleRepeated chemogenetic stimulation is often employed to study circuit function and behavior. Chronic or repeated agonist administration can result in homeostatic changes, but this has not been extensively studied with designer receptors exclusively activated by designer drugs (DREADDs).
objectivesWe sought to evaluate the impact of repeated DREADD activation of dopaminergic (DA) neurons on basal behavior, amphetamine response, and spike firing. We hypothesized that repeated DREADD activation would mimic compensatory effects that we observed with genetic manipulations of DA neurons.
methodsExcitatory hM3D(Gq) DREADDs were virally expressed in adult TH-Cre and WT mice. In a longitudinal design, clozapine N-oxide (CNO, 1.0 mg/kg) was administered repeatedly. We evaluated basal and CNO- or amphetamine (AMPH)-induced locomotion and stereotypy. DA neuronal activity was assessed using in vivo single-unit recordings.
resultsAcute CNO administration increased locomotion, but basal locomotion decreased after repeated CNO exposure in TH-Cre
conclusionsWe found that repeated DREADD activation of DA neurons evokes homeostatic changes that should be factored into the interpretation of chronic DREADD applications and their impact on circuit function and behavior. These effects are likely to also be seen in other neuronal systems and underscore the importance of studying neuroadaptive changes with chronic or repeated DREADD activation.
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