GIUV2015-237
Our team has been working for approximately 20 years on several research lines related to different neuropharmacological and neurochemical aspects of the treatment of alcoholism relapse. One of our current research lines focuses on the study and analysis of drugs for the treatment of relapse that act on new potential therapeutic targets. In this sense, our research has allowed us to demonstrate that acetaldehyde sequestration, using D-Penicillamine (DP), is an effective and promising therapeutic strategy to block relapse in alcohol consumption. In addition, we have demonstrated the advantage of the combined use of PD with naltrexone (an opioid receptor antagonist currently used in the treatment of relapse in alcohol dependence, although with very limited efficacy) compared to single treatment with naltrexone for relapse prevention. We are currently evaluating the effectiveness of a new drug in alcoholism relapse: N-acetylcysteine, an amino acid that could potentially normalise the alteration of glutamatergic homeostasis caused by ethanol at the level of GLT-1 and xCT transporters. Our second research line is focused on establishing the mechanistic basis underlying the action of...Our team has been working for approximately 20 years on several research lines related to different neuropharmacological and neurochemical aspects of the treatment of alcoholism relapse. One of our current research lines focuses on the study and analysis of drugs for the treatment of relapse that act on new potential therapeutic targets. In this sense, our research has allowed us to demonstrate that acetaldehyde sequestration, using D-Penicillamine (DP), is an effective and promising therapeutic strategy to block relapse in alcohol consumption. In addition, we have demonstrated the advantage of the combined use of PD with naltrexone (an opioid receptor antagonist currently used in the treatment of relapse in alcohol dependence, although with very limited efficacy) compared to single treatment with naltrexone for relapse prevention. We are currently evaluating the effectiveness of a new drug in alcoholism relapse: N-acetylcysteine, an amino acid that could potentially normalise the alteration of glutamatergic homeostasis caused by ethanol at the level of GLT-1 and xCT transporters. Our second research line is focused on establishing the mechanistic basis underlying the action of ethanol on the mesolimbic system. Activation of dopaminergic (DA) neurons in the ventral tegmental area (VTA) is an initial event necessary for the development of drug addiction. Although the mechanisms involved in this activation are known in detail for drugs such as psychostimulants, opiates or nicotine, the same does not apply to ethanol. Our research aims to specify certain aspects of the mechanism by which ethanol takes over this important dopaminergic pathway. Our group has suggested that the action of ethanol on the mesolimbic system is dual: on the one hand, those responsible for the activation of this system would be the products derived from the brain metabolism of ethanol and, among them, salsolinol (a product derived from acetaldehyde and dopamine) which would act through mu-type opioid receptors. On the other hand, the non-metabolised fraction of ethanol would act in the opposite direction, limiting the activation of DA neurons by promoting of GABAergic inhibition of these neurons. This knowledge may be useful for identifying new therapeutic targets, as well as developing new pharmacological strategies for the treatment of alcoholism. Currently, two new reseach lines have been incorporated into our group. In the study of relapse, certain factors that may promote relapse and/or the risk of suffering a new drug use disorder play a major role. Among these factors, we are currently analysing how the presence of pain alters the mesocorticolimbic system and, in particular, the pharmacology of opioid receptors. These neurobiological alterations may lead to the development of comorbidities, such as negative-affective states. Negative-affective states are a known component that can either increase the risk of suffering a drug use disorder or precipitate relapse in their consumption, including alcohol. In this sense, we are analysing the neurobiological alterations that allow us to detect new therapeutic targets which, in a more selective and effective way, can prevent initiation or relapse in drug use. As a result of the analysis of these new targets, we are developing pharmaceutical forms that allow us to vectorise treatments to the central nervous sytem, thus limiting the appearance of side effects on other organs. Finally, the last research line incorporated analyses the role of microglia in the regulation of the expression, internalisation and function of opioid receptors in the mesocorticolimbic system in pathological situations such as the presence of pain and/or drug use disorder.
[Read more][Hide]
[Read more][Hide]
- Estudio de nuevas dianas terapeuticas en el tratamiento de la recaida en el paciente alcoholico
- Desentrañar los distintos aspectos neuroquimicos del etanol en el Sistema Nervioso Central
- Analizar las alteraciones inducidas por la presencia del dolor en el Sistema Mesocorticolimbico y sus consecuencias sobre los estados afectivos negativos y la recaida en el consumo de drogas
- Desarrollo de formes farmaceuticas que permitan la vectorizacion de las nuevas dianas terapeuticas a sistema nervioso central.
- Analizar los mecanismos de comunicacion microglia-neurona que alteran la expresion, internalizacion y/o funcion de los receptores opioides.
- Development of novel therapeutic drugs to prevent relapse in alcoholics.Development of new therapeutic strategies for the treatment of relapse in alcoholic patients. Pre-clinical trials with D-Penicillamine, a sequestering agent of an ethanol metabolite, acetaldehyde.
- Neurobiological mechanisms involved in alcohol addiction.Our research line focuses on establishing the mechanistic basis underlying the action of ethanol on the mesolimbic system.
- Alteracions del sistema mesocorticolimbic induïdes per dolor: paper en els estats afectius negatius i en el trastorn d'ús de drogues.The presence of pain alters the mesocorticolimbic system and, in particular, the pharmacology of opioid receptors, promoting the appearance of comorbidities as negative affective states. These negative affective states are a risk factor for a drug use disorders, including alcohol. In this respect, we are analysing pain-induced neurobiological alterations to find new therapeutic targets in a more selective and effective way for these cases. As a result of the analysis of these new targets, we are also developing pharmaceutical forms that allow treatments to be vectorized to the central nervous system, limiting the incidence of side effects on other organs.
- Role of microglial cells in the regulation of the expression, internalization and function of the opioid receptors in the mesocorticolimbic system.Microglia, and their activity in the nervous system, have been shown to have a role beyond immune function. In fact, in this line we analyse microglia-neuron communication and how this communication can regulate the expression, internalisation and/or function of opioid receptors in the mesocorticolimbic system in pathological situations.
| Name | Nature of participation | Entity | Description |
|---|---|---|---|
| ANA POLACHE VENGUT | Director | Universitat de València | |
| Research team | |||
| TEODORO ANTONIO ZORNOZA SABINA | Member | Universitat de València | |
| LUIS FCO GRANERO MACIA | Member | Universitat de València | |
| MARIA JOSE CANO CEBRIAN | Member | Universitat de València | |
| LUCIA TERESA HIPOLITO CUBEDO | Collaborator | Universitat de València | |
- -
- Pharmacy, Pharmaceutical Technology and Parasitology
- Recaída; alcoholismo; agentes secuestrantes del acetaldehido
- Acetaldehído; receptores opiodes mu; receptores GABAA ; área tegmental ventral; salsolinol; nucleo accumbens
- Dolor, sistema mesocorticolímbico, dopamina, opioides, alcohol, liposomas, vectorización
- Microglía, Astrocitos
