Person: Alén Fariñas, Francisco
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First Name
Francisco
Last Name
Alén Fariñas
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Odontología
Department
Psicobiología y Metodología en Ciencias del Comportamiento
Area
Psicobiología
Identifiers
6 results
Search Results
Now showing 1 - 6 of 6
Item Bupropion, a possible antidepressant without negative effects on alcohol relapse(European Neuropsychopharmacology, 2019) Alén Fariñas, Francisco; Gómez De Heras, María Raquel; Orio Ortiz, Laura; Rodríguez De Fonseca, Fernando Antonio; Antonio Ballesta; Rocío Arco; Antonio Vargas; Pablo Romero-Sanchiz; Raquel Nogueira-Arjona; María Antón; Mayte Ramírez-López; Antonia Serrano; Francisco Javier Pavón; Juan SuárezRationale: the role that antidepressants play on alcohol consumption is not well understood. Previous studies have reported that treatment with a Selective Serotonin Reuptake Inhibitor (SSRIs) increases alcohol consumption in an animal model of relapse, however it is unknown whether this effect holds for other antidepressants such as the atypical dopamine/norepinephrine reuptake inhibitors (SNDRI). Objectives: the main goal of the present study was to compare the effects of two classes of antidepressants drugs, bupropion (SNDRI) and fluoxetine (SSRI), on alcohol consumption during relapse. Since glutamatergic and endocannabinoid signaling systems plays an important rolein alcohol abuse and relapse, we also evaluated the effects of both antidepressants ontheexpression of the main important genes and proteins of both systems in the prefrontal cortex,a critical brain region in alcohol relapse. Methods: rats were trained to self-administered alcohol. During abstinence, rats received a14d-treatment with vehicle, fluoxetine (10 mg/kg) or bupropion (20 mg/kg), and we evaluatedalcohol consumption during relapse for 3 weeks. Samples of prefrontal cortex were taken toevaluate the mRNA and protein expression of the different components of glutamatergic andendocannabinoid signaling systems. Results: fluoxetine treatment induced a long-lasting increase in alcohol consumption during relapse, an effect that was not observed in the case of bupropion treatment. The observed increases in alcohol consumption were accompanied by distinct alterations in the glutamate and endocannabinoid systems. Conclusions: our results suggest that SSRIs can negatively impact alcohol consumption in relapse while SNDRIs have no effects. The observed increase in alcohol consumption are accompanied by functional alterations in the glutamatergic and endocannabinoid systems. This finding could open new strategies for the treatment of depression in patients with alcohol use disorders.Item Increased plasma oleoylethanolamide and palmitoleoylethanolamide levels correlate with inflammatory changes in alcohol binge drinkers: the case of HMGB1 in women(Addiction biology, 2017) Antón, María; Rodríguez‐González, Alicia; Rodríguez Rojo, Inmaculada Concepción; Pastor, Antoni; Correas Marín, María De Los Ángeles; Serrano, Antonia; Ballesta, Antonio; Alén Fariñas, Francisco; Gómez De Heras, María Raquel; Torre, Rafael de la; Rodríguez De Fonseca, Fernando Antonio; Orio Ortiz, LauraAlcohol binge drinking is a heavy pattern of alcohol consumption increasingly used by young people. In a previous study, we reported that young drinkers with a 2‐year history of binge alcohol consumption had an overactivation of the innate immune system and peripheral inflammation when compared with controls. In the present study, we measured several biolipids that are fatty acid derivatives belonging to the acylethanolamide or 2‐acylglycerol families in the plasma of the same subjects (n = 42; 20 men and 22 women). We found that during abstinence, alcohol binge drinkers had elevated plasma levels of oleoylethanolamide, palmitoleoylethanolamide, arachidonoylethanolamide, dihomo‐γ‐linolenoyl ethanolamide and linoleoyl ethanolamide, which positively correlated with changes in the mRNA expression of key inflammatory markers in peripheral blood mononuclear cells, such as toll‐like receptors (TLR4), pro‐inflammatory cytokines/chemokines interleukin‐1 beta, interleukin‐6 and monocyte chemoattractant protein‐1, and cyclooxygenase‐2. Additionally, plasma oleoylethanolamide positively correlated with plasma levels of high mobility group box‐1, which is a danger‐associated molecular pattern and an endogenous TLR4 agonist, specifically in female alcohol binge drinkers. No changes were observed in 2‐acylglycerols in alcohol binge drinkers, although sex‐related differences in these bioactive lipids as well as in palmitoleoylethanolamide and docosatetraenoylethanolamide levels were detected. These results extend the previous clinical findings observed in patients diagnosed with long‐term alcohol use disorder to young users and suggest a prominent role for these lipids in the response to acute alcohol exposure.Item Rethinking the Use of Antidepressants to Treat Alcohol Use Disorders and Depression Comorbidity: The Role of Neurogenesis(Antidepressants - Preclinical, Clinical and Translational Aspects, 2019) Alén Fariñas, Francisco; Gómez De Heras, María Raquel; Orio Ortiz, Laura; Rodríguez De Fonseca, Fernando Antonio; Ballesta, AntonioPatients with alcohol use disorders (AUDs) are frequently treated with antidepressant drugs (ADs), but clinical evidence of their efficacy is contradictory. Considering that ADs are thought to produce their therapeutic effects partially by increasing hippocampal plasticity and neurogenesis (HN), and that both AUDs and depression share a potential for the disruption of these neuroplastic processes, one could reasonably wonder whether the poor efficacy of AD treatment could be explained by the inability of these drugs to exert their proper action in patients suffering from AUD or depression. In order to further clarify this question, this chapter aims to examine available data regarding the effect of ADs on behavioral and HN alterations related to alcohol abstinence, as a key period in which the treatment would be implemented and in which their potential effects on alcohol-related problems remain under controversy.Item Sex-Dimorphic Behavioral Alterations and Altered Neurogenesis in U12 Intron Splicing-Defective Zrsr1 Mutant Mice(International Journal of Molecular Sciences, 2019) Alén Fariñas, Francisco; Gómez-Redondo, Isabel; Rivera, Patricia; Suárez, Juan; Ramos-Ibeas, Priscila; Pericuesta, Eva; Fernández-González, Raul; Perez-Cerezales, Serafín; Horiuchi, Keiko; Orio Ortiz, Laura; Rodriguez de Fonseca, Fernando; Gutiérrez-Adán, AlfonsoMutant mice with respect to the splicing factor Zrsr1 present altered spermatogenesis and infertility. To investigate whether Zrsr1 is involved in the homeostatic control that the hypothalamus exerts over reproductive functions, we first analyzed both differential gene and isoform expression and alternative splicing alterations in Zrsr1 mutant (Zrsr1mu) hypothalamus; second, we analyzed the spontaneous and social behavior of Zrsr1mu mice; and third, we analyzed adult cell proliferation and survival in the Zrsr1mu hypothalamus. The Zrsr1mu hypothalamus showed altered expression of genes and isoforms related to the glutathione metabolic process, synaptonemal complex assembly, mRNA transport, and altered splicing events involving the enrichment of U12-type intron retention (IR). Furthermore, increased IR in U12-containing genes related with the prolactin, progesterone, and gonadotropin-releasing hormone (GnRH) reproductive signaling pathway was observed. This was associated with a hyperactive phenotype in both males and females, with an anxious phenotype in females, and with increased social interaction in males, instead of the classical aggressive behavior. In addition, Zrsr1mu females but not males exhibited reduced cell proliferation in both the hypothalamus and the subventricular zone. Overall, these results suggest that Zrsr1 expression and function are relevant to organization of the hypothalamic cell network controlling behavior.Item Abrupt cessation of reboxetine along alcohol deprivation results in alcohol intake escalation after reinstatement of drinking(2020) Ballesta, Antonio; Arco, Rocío; Vadas, Evelyn; Decara, Juan; Vargas, Antonio; Ramírez‐López, Mayte; Serrano, Antonia; Suárez, Juan; Rodríguez De Fonseca, Fernando Antonio; Pavón Carrasco, Francisco Javier; Gómez De Heras, María Raquel; Orio Ortiz, Laura; Alén Fariñas, FranciscoAbstract Major depression (MD) is a frequent comorbidity in alcohol use disorder (AUD) patients. Antidepressant prescription is often limited by poor clinical outcomes or unwanted side effects in comorbid AUD‐MD patients. Recent studies suggest that abrupt cessation of selective serotonin reuptake inhibitors antidepressant treatment increases alcohol consumption after an alcohol deprivation period in rats. However, the appearance of this effect after the treatment with selective noradrenaline reuptake inhibitors (SNRIs) is not known. Here, we report that interruption of subchronic (14 days) treatment with the SNRIs reboxetine (15 mg/kg/day intraperitoneally) resulted in escalation of ethanol intake when the animals resume alcohol self‐administration. This effect of reboxetine treatment cessation was associated with a profound deactivation of the endocannabinoid/acylethanolamide signaling system in the prefrontal cortex but not in the dorsal hippocampus, as reflected by the decrease in the protein expression of the cannabinoid CB1 receptor, the PPARα receptor, the 2‐arachidonoylglycerol synthesizing enzymes DAGLα and DGALβ, and the endocanabinoid degrading enzyme MAGL. This was associated with dysregulation of the expression of glutamic acid receptors GluN1, GluA1, and mGlu5 in the medial prefrontal cortex and the dorsal hippocampus of the animals exposed to reboxetine. The present results further support the idea that abrupt cessation of antidepressant therapy along alcohol deprivation time can boost alcohol intake after relapse through mechanisms associated with endocannabinoid/glutamate signaling dysregulation. This finding might be relevant for patients suffering AUD/MD comorbidity where antidepressant therapy must be monitored with caution for avoiding unwanted side effects if adherence to the treatment is not fully achieved.Item Antianhedonic and Antidepressant Effects of Affron®, a Standardized Saffron (Crocus Sativus L.) Extract(Molecules, 2020) Orio Ortiz, Laura; Alén Fariñas, Francisco; Ballesta García, Antonio; Martín Martín, Raquel; Gómez De Heras, María RaquelAnxiety and depression have high prevalence in the general population, affecting millions of people worldwide, but there is still a need for effective and safe treatments. Nutritional supplements have recently received a lot of attention, particularly saffron. Thus, several pre-clinical studies support a beneficial role for bioactive compounds, such as saffron, in anxiety and depression. Here we used an animal model of depression based on social isolation to assess the effects of affron®, a standardized saffron extract containing ≥3.5% of total bioactive compounds safranal and crocin isomers. Affron® was administered both through the oral and the intraperitoneal routes, and several tasks related to anxiety and depression, such as the elevated plus maze, the forced swimming test or the sucrose preference test, were assessed. These tasks model key features of depressive states and anxious states relating to fear, behavioral despair or anhedonia, the lack of motivation and/or pleasure from everyday activities, respectively. Animals receiving oral affron® displayed behaviors congruent with improvements in their anxious/depressive state, showing the enhanced consumption of a sweet solution, as well as an increase in certain escape responses in the forced swimming test. Our data support a beneficial role for oral saffron in anxious/depressive states.