Back to Search
Start Over
Chronic Administrations of Guanfacine on Mesocortical Catecholaminergic and Thalamocortical Glutamatergic Transmissions
- Source :
- International Journal of Molecular Sciences, Volume 22, Issue 8, International Journal of Molecular Sciences, Vol 22, Iss 4122, p 4122 (2021)
- Publication Year :
- 2021
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2021.
-
Abstract
- It has been established that the selective α2A adrenoceptor agonist guanfacine reduces hyperactivity and improves cognitive impairment in patients with attention-deficit/hyperactivity disorder (ADHD). The major mechanisms of guanfacine are considered to involve the activation of the postsynaptic α2A adrenoceptor of glutamatergic pyramidal neurons in the frontal cortex, but the effects of chronic guanfacine administration on catecholaminergic and glutamatergic transmissions associated with the orbitofrontal cortex (OFC) are yet to be clarified. The actions of guanfacine on catecholaminergic transmission, the effects of acutely local and systemically chronic (for 7 days) administrations of guanfacine on catecholamine release in pathways from the locus coeruleus (LC) to OFC, the ventral tegmental area (VTA) and reticular thalamic-nucleus (RTN), from VTA to OFC, from RTN to the mediodorsal thalamic-nucleus (MDTN), and from MDTN to OFC were determined using multi-probe microdialysis with ultra-high performance liquid chromatography. Additionally, the effects of chronic guanfacine administration on the expression of the α2A adrenoceptor in the plasma membrane fraction of OFC, VTA and LC were examined using a capillary immunoblotting system. The acute local administration of therapeutically relevant concentrations of guanfacine into the LC decreased norepinephrine release in the OFC, VTA and RTN without affecting dopamine release in the OFC. Systemically, chronic administration of therapeutically relevant doses of guanfacine for 14 days increased the basal release of norepinephrine in the OFC, VTA, RTN, and dopamine release in the OFC via the downregulation of the α2A adrenoceptor in the LC, OFC and VTA. Furthermore, systemically, chronic guanfacine administration did not affect intrathalamic GABAergic transmission, but it phasically enhanced thalamocortical glutamatergic transmission. The present study demonstrated the dual actions of guanfacine on catecholaminergic transmission—acute attenuation of noradrenergic transmission and chronic enhancement of noradrenergic transmission and thalamocortical glutamatergic transmission. These dual actions of guanfacine probably contribute to the clinical effects of guanfacine against ADHD.
- Subjects :
- Male
Synaptic Transmission
Rats, Sprague-Dawley
GABA
Thalamus
Adrenergic alpha-2 Receptor Agonists
Medicine
Biology (General)
Spectroscopy
gamma-Aminobutyric Acid
guanfacine
Catecholaminergic
musculoskeletal, neural, and ocular physiology
General Medicine
Computer Science Applications
Guanfacine
Ventral tegmental area
Chemistry
medicine.anatomical_structure
L-glutamate
dopamine
psychological phenomena and processes
medicine.drug
QH301-705.5
Glutamic Acid
Prefrontal Cortex
attention-deficit/hyperactivity disorder
Catalysis
Article
norepinephrine
Inorganic Chemistry
Norepinephrine
Glutamatergic
Dopamine
Receptors, Adrenergic, alpha-2
mental disorders
Animals
Physical and Theoretical Chemistry
Molecular Biology
QD1-999
business.industry
Organic Chemistry
Rats
α2A adrenoceptor
nervous system
Attention Deficit Disorder with Hyperactivity
Catecholamine
Locus coeruleus
business
Neuroscience
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....ade85aa201df6542b5320a274e04baf4
- Full Text :
- https://doi.org/10.3390/ijms22084122