Ethanol-Dependent Synthesis of Salsolinol in the Posterior Ventral Tegmental Area as Key Mechanism of Ethanol’s Action on Mesolimbic Dopamine
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Valentina Bassareo; Valentina Bassareo
Derived by OpenAIRE algorithms or harvested from 3rd party repositories Valentina Bassareo in OpenAIRE
Riccardo Maccioni; Riccardo Maccioni
Harvested from ORCID Public Data File Riccardo Maccioni in OpenAIRE
Pierluigi Caboni; Pierluigi Caboni
Derived by OpenAIRE algorithms or harvested from 3rd party repositories Pierluigi Caboni in OpenAIRE
Cristina Manis; Cristina Manis
Harvested from ORCID Public Data File Cristina Manis in OpenAIRE
Valentina Bassareo; Valentina Bassareo
Derived by OpenAIRE algorithms or harvested from 3rd party repositories Valentina Bassareo in OpenAIRE
Riccardo Maccioni; Riccardo Maccioni
Harvested from ORCID Public Data File Riccardo Maccioni in OpenAIRE
Pierluigi Caboni; Pierluigi Caboni
Derived by OpenAIRE algorithms or harvested from 3rd party repositories Pierluigi Caboni in OpenAIRE
Cristina Manis; Cristina Manis
Harvested from ORCID Public Data File Cristina Manis in OpenAIRE
Elio Acquas; Elio Acquas
Derived by OpenAIRE algorithms or harvested from 3rd party repositories Elio Acquas in OpenAIRE
Ethanol-Dependent Synthesis of Salsolinol in the Posterior Ventral Tegmental Area as Key Mechanism of Ethanol’s Action on Mesolimbic Dopamine
Abnormal consumption of ethanol, the ingredient responsible for alcoholic drinks’ addictive liability, causes millions of deaths yearly. Ethanol’s addictive potential is triggered through activation, by a still unknown mechanism, of the mesolimbic dopamine (DA) system, part of a key motivation circuit, DA neurons in the posterior ventral tegmental area (pVTA) projecting to the ipsilateral nucleus accumbens shell (AcbSh). The present in vivo brain microdialysis study, in dually-implanted rats with one probe in the pVTA and another in the ipsilateral or contralateral AcbSh, demonstrates this mechanism. As a consequence of the oral administration of a pharmacologically relevant dose of ethanol, we simultaneously detect a) in the pVTA, a substance, 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol), untraceable under control conditions, product of condensation between DA and ethanol’s first by-product, acetaldehyde; and b) in the AcbSh, a significant increase of DA release. Moreover, such newly generated salsolinol in the pVTA is responsible for increasing AcbSh DA release via μ opioid receptor (μOR) stimulation. In fact, inhibition of salsolinol’s generation in the pVTA or blockade of pVTA μORs prevents ethanol-increased ipsilateral, but not contralateral, AcbSh DA release. This evidence discloses the long-sought key mechanism of ethanol’s addictive potential and suggests the grounds for developing preventive and therapeutic strategies against abnormal consumption.
Italy
acetaldehyde, brain microdialysis, dopamine, ethanol, μ opioid receptors, nucleus accumbens shell, posterior ventral tegmental area, salsolinol, General Neuroscience, Neurosciences. Biological psychiatry. Neuropsychiatry, brain microdialysis, acetaldehyde; brain microdialysis; dopamine; ethanol; m opioid receptors; nucleus accumbens shell; posterior ventral tegmental area; salsolinol, ethanol, dopamine, nucleus accumbens shell, μ opioid receptors, acetaldehyde, RC321-571, Neuroscience
acetaldehyde, brain microdialysis, dopamine, ethanol, μ opioid receptors, nucleus accumbens shell, posterior ventral tegmental area, salsolinol, General Neuroscience, Neurosciences. Biological psychiatry. Neuropsychiatry, brain microdialysis, acetaldehyde; brain microdialysis; dopamine; ethanol; m opioid receptors; nucleus accumbens shell; posterior ventral tegmental area; salsolinol, ethanol, dopamine, nucleus accumbens shell, μ opioid receptors, acetaldehyde, RC321-571, Neuroscience
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