Molecular mechanisms of tolerance to and withdrawal of GABA(A) receptor modulators
Giovanni Biggio1, Laura Dazzi, Francesca Biggio
1Department of Experimental Biology "Bernardo Loddo,", Center of Excellence for the Neurobiology of Dependence, University of Cagliari, 09123, Italy. biggio@unica.it
Abstract:
Here, we summarize recent data pertaining to the effects of GABA(A) receptor modulators on the receptor gene expression in order to elucidate the molecular mechanisms behind tolerance and dependence induced by these drugs. Drug selectivity and intrinsic activity seems to be important to evidence at the molecular level the GABA(A) receptor tolerance. On the contrary, we suggested that all drug tested are equally potentially prone to induce dependence. Our results demonstrate that long-lasting exposure of GABA(A) receptors to endogenous steroids, benzodiazepines and ethanol, as well as their withdrawal, induce marked effects on receptor structure and function. These results suggest the possible synergic action between endogenous steroids and these drugs in modulating the functional activity of specific neuronal populations. We report here that endogenous steroids may play a crucial role in the action of ethanol on dopaminergic neurons.
More Related Videos
07:16Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
09:29Investigating Drivers of Antireward in Addiction Behavior with Anatomically Specific Single-Cell Gene Expression Methods
Published on: August 4, 2022
Related Concept Videos
GPCR Desensitization
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Desensitization and Tachyphylaxis
Several...
CNS Depressants: Alcohol and Nicotine
Analgesia and Pain Management
Antiepileptic Drugs: GABAergic Pathway Potentiators
The key GABA pathway potentiators used in epilepsy management are as follows.
Benzodiazepines are a well-known class of drugs used for their...
