BEHAVIORAL AND MOLECULAR EFFECTS OF COMBINED 5-HT2A RECEPTOR AGONISM AND ANODAL TDCS IN A PRECLINICAL MODEL OF COMPULSIVE ALCOHOL DRINKING

Clinical evidence indicates a high comorbidity between alcohol use disorder and obsessive–compulsive symptoms, pointing toward overlapping neurobiological substrates. The serotonin 5-HT2A receptor has been implicated in compulsive spectrum disorders, and combined approaches using transcranial direct current stimulation (tDCS) with pharmacological treatments such as SSRIs. Based on this, the objective of the study was to evaluate the therapeutic potential of tDCS, psychedelic drug administration, and their combined treatment in the compulsive alcohol drinking population and to assess treatment-induced changes in genetic biomarkers using RNAscope HiPlex. Male Wistar rats were exposed to alcohol in a preclinical compulsivity model known as Schedule-Induced Polydipsia (SIP) and classified as high alcohol drinkers (HAD) or low alcohol drinkers (LAD) based on their alcohol drinking. Following group formation, animals received a single administration of DOI or saline combined with either anodal tDCS or sham stimulation applied over the frontal cortex. Behavioral assessments were conducted 1 and 24 hours after treatment. Subsequently, gene expression of markers associated with the serotonergic, glutamatergic, GABAergic, dopaminergic, endocannabinoid, and synaptic plasticity markers in the prelimbic and infralimbic areas was analyzed. The results will be discussed regarding the potential of this combined intervention to reduce compulsive alcohol consumption and modulate the neuronal circuits implicated.
Funding: PID2022-139286NB-I00 PGC, MCIN/AEI/10.13039/ 501100011033; PND-2022l024 PNSD, MISAN; SUBV23/00027, MIC, DGOJ, Gobierno de España and Fondos Feder; and PPIT-UAL, Junta de Andalucía-ERDF 2021-2027. Objective RSO1.1. Programme: 54.A. Programme scholarship: I was supported by Consejería de Transformación Económica, Industria, Conocimiento y Universidades, Junta de Andalucía, PAIDI (2020).