Alpha-1 Adrenergic Receptors Modulate Glutamate and GABA Neurotransmission onto Ventral Tegmental Dopamine Neurons during Cocaine Sensitization

Autor: Bermary Santos-Vera, Maria E. Velez-Hernandez, Maria Carolina Velasquez-Martinez, Carlos A. Jiménez-Rivera, Rafael Vázquez-Torres
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Patch-Clamp Techniques
alpha1 adrenergic receptors
Action Potentials
lcsh:Chemistry
GABA
0302 clinical medicine
Cocaine
lcsh:QH301-705.5
Spectroscopy
Sensitization
gamma-Aminobutyric Acid
Chemistry
musculoskeletal
neural
and ocular physiology
Glutamate receptor
General Medicine
dopamine neurons
3. Good health
Computer Science Applications
cocaine sensitization
Ventral tegmental area
medicine.anatomical_structure
Excitatory postsynaptic potential
psychological phenomena and processes
medicine.drug
Signal Transduction
Presynaptic Terminals
Glutamic Acid
glutamate
Neurotransmission
Inhibitory postsynaptic potential
Models
Biological
Catalysis
Article
Inorganic Chemistry
03 medical and health sciences
Glutamatergic
Cocaine-Related Disorders
Dopamine
Receptors
Adrenergic
alpha-1
mental disorders
medicine
Animals
Physical and Theoretical Chemistry
Molecular Biology
Dopaminergic Neurons
Organic Chemistry
Ventral Tegmental Area
noradrenergic inputs
Rats
Disease Models
Animal
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
nervous system
Neuroscience
030217 neurology & neurosurgery
Zdroj: International Journal of Molecular Sciences
Volume 21
Issue 3
International Journal of Molecular Sciences, Vol 21, Iss 3, p 790 (2020)
ISSN: 1422-0067
Popis: The ventral tegmental area (VTA) plays an important role in the reward and motivational processes that facilitate the development of drug addiction. Presynaptic &alpha
1-AR activation modulates glutamate and Gamma-aminobutyric acid (GABA) release. This work elucidates the role of VTA presynaptic &alpha
1-ARs and their modulation on glutamatergic and GABAergic neurotransmission during cocaine sensitization. Excitatory and inhibitory currents (EPSCs and IPSCs) measured by a whole cell voltage clamp show that &alpha
1-ARs activation increases EPSCs amplitude after 1 day of cocaine treatment but not after 5 days of cocaine injections. The absence of a pharmacological response to an &alpha
1-ARs agonist highlights the desensitization of the receptor after repeated cocaine administration. The desensitization of &alpha
1-ARs persists after a 7-day withdrawal period. In contrast, the modulation of &alpha
1-ARs on GABA neurotransmission, shown by decreases in IPSCs&rsquo
amplitude, is not affected by acute or chronic cocaine injections. Taken together, these data suggest that &alpha
1-ARs may enhance DA neuronal excitability after repeated cocaine administration through the reduction of GABA inhibition onto VTA dopamine (DA) neurons even in the absence of &alpha
1-ARs&rsquo
function on glutamate release and protein kinase C (PKC) activation. &alpha
1-AR modulatory changes in cocaine sensitization increase our knowledge of the role of the noradrenergic system in cocaine addiction and may provide possible avenues for therapeutics.
Databáze: OpenAIRE
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