Back to Search
Start Over
Differential effects of chemogenetic inhibition of dopamine and norepinephrine neurons in the mouse 5-choice serial reaction time task
- Source :
- Progress in Neuro-Psychopharmacology and Biological Psychiatry. 90:264-276
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Attention-deficit/hyperactivity disorder (ADHD) is a psychiatric disorder characterized by inattention, aberrant impulsivity, and hyperactivity. Although the underlying pathophysiology of ADHD remains unclear, dopamine and norepinephrine signaling originating from the ventral tegmental area (VTA) and locus coeruleus (LC) is thought to be critically involved. In this study, we employ Designer Receptor Exclusively Activated by Designer Drugs (DREADDs) together with the mouse 5-Choice Serial Reaction Time Task (5-CSRTT) to investigate the necessary roles of these catecholamines in ADHD-related behaviors, including attention, impulsivity, and motivation. By selective inhibition of tyrosine hydroxylase (TH)-positive VTA dopamine neurons expressing the Gi-coupled DREADD (hM4Di), we observed a marked impairment of effort-based motivation and subsequently speed and overall vigor of responding. At the highest clozapine N-oxide (CNO) dose tested (i.e. 2 mg/kg) to activate hM4Di, we detected a reduction in locomotor activity. DREADD-mediated inhibition of LC norepinephrine neurons reduced attentional performance in a variable stimulus duration test designed to increase task difficulty, specifically by increasing trials omissions, reducing mean score, and visual processing speed. These findings show that VTA dopamine and LC norepinephrine neurons differentially affect attention, impulsive and motivational control. In addition, this study highlights how molecular genetic probing of selective catecholamine circuits can provide valuable insights into the mechanisms underlying ADHD-relevant behaviors.
- Subjects :
- Male
Serial reaction time
Dopamine
Mice, Transgenic
Receptors, Cell Surface
Motor Activity
Neuropsychological Tests
Stimulus (physiology)
Impulsivity
Norepinephrine
03 medical and health sciences
0302 clinical medicine
medicine
Animals
Attention
Biological Psychiatry
Neurons
Pharmacology
Motivation
Tyrosine hydroxylase
business.industry
Ventral Tegmental Area
030227 psychiatry
Mice, Inbred C57BL
Ventral tegmental area
medicine.anatomical_structure
Genetic Techniques
Impulsive Behavior
Catecholamine
Locus coeruleus
medicine.symptom
business
Neuroscience
medicine.drug
Subjects
Details
- ISSN :
- 02785846
- Volume :
- 90
- Database :
- OpenAIRE
- Journal :
- Progress in Neuro-Psychopharmacology and Biological Psychiatry
- Accession number :
- edsair.doi.dedup.....bf8d5de9f449a0be076b6dc001930aeb