1. Molecular mechanisms of tolerance to and withdrawal of GABAA receptor modulators
- Author
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Enrico Sanna, Giovanni Biggio, Luisa Mancuso, Paolo Follesa, Laura Dazzi, Francesca Biggio, Giuseppe Talani, Maria Cristina Mostallino, and Fabio Busonero
- Subjects
Cell Extracts ,Male ,Patch-Clamp Techniques ,Intrinsic activity ,Microdialysis ,Pharmacology ,Membrane Potentials ,GABAA-rho receptor ,Rats, Sprague-Dawley ,Benzodiazepines ,Cerebellum ,Electrochemistry ,Drug Interactions ,Pharmacology (medical) ,Receptor ,Cells, Cultured ,Chromatography, High Pressure Liquid ,gamma-Aminobutyric Acid ,media_common ,Neurons ,Reverse Transcriptase Polymerase Chain Reaction ,GABAA receptor ,Dopaminergic ,Drug Tolerance ,Substance Withdrawal Syndrome ,Psychiatry and Mental health ,Neurology ,Steroids ,medicine.drug ,Drug ,Neuroactive steroid ,Tyrosine 3-Monooxygenase ,media_common.quotation_subject ,Immunoblotting ,Biology ,Time ,Dopamine ,medicine ,Animals ,RNA, Messenger ,Biological Psychiatry ,Dose-Response Relationship, Drug ,Ethanol ,Cell Membrane ,Neural Inhibition ,Receptors, GABA-A ,Rats ,Animals, Newborn ,Gene Expression Regulation ,Oocytes ,Neurology (clinical) - 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.
- Published
- 2003