Investigation of the participation of hippocampal projections to infralimbic cortex and nucleus acumbens in the context-induced reinstatement of ethanol seeking

• Grant number: 21/00838-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2021
• End date: November 30, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Fabio Cardoso Cruz
• Grantee: Alexia dos Anjos Santos
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 18/15505-4 - Neurobiology study of relapse to alcohol and cocaine seeking: identification of plasticity in neuronal ensembles that encodes addiction-related memories, AP.JP2
• Associated scholarship(s): 23/09647-9 - Investigation of sex-specific mechanisms underlying anti-stress nociceptin and norepinephrine interactions on synaptic transmission and neuronal functions in the central amygdala in ethanol dependence and withdrawal, BE.EP.DR

Abstract

Ethanol is one of the most used legal psychoactive substances in the world and its repeated use can lead to the development of addiction and even death. In the treatment of ethanol dependence, one of the main challenges is to reduce relapse rates. One of the factors that increase the likelihood of an individual relapsing is the individual's exposure to contextual cues associated with use. This happens because, during the use of the drug, the individual learns to associate the rewarding effects of the substance with the environment of use. With repeated use, these associations acquire salience, thus, the simple exposure to the cues triggers environmental fissure, leading to the reestablishment of the drug seeking behavior. In animals, this process can be studied through the model of reinstatement of operative self-administration induced by the context or ABA renewal. Evidence shows that the use of this behavioral model associated with molecular techniques, contributes to the elucidation of the neurobiological mechanisms responsible for relapse. However, the neurobiology of relapse to the use of ethanol is not fully understood. Studies in rodents with the participation of the hippocampus (structure of the limbic system responsible for the combination of contextual and emotional information) in the contextual reinstatement of drug seeking. In addition, their projections to other brain regions, such as the infralimbic cortex and the nucleus accumbens, are also important for the contextual reinstatement of drug seeking. However, the involvement of these routes in the contextual reinstatement of ethanol seeking search has not yet been fully elucidated. Thus, the aim of this project will be: I) to identify phenotyping and the percentage of small neural cells selectively activated in the hippocampus, during the reinstatement of context-induced self-administration of ethanol; II) to evaluate the participation of the dorsal hippocampus projections to the infralimbic cortex and nucleus accumbens in the reinstatement of context-induced ethanol seeking behavior, using the retrograde marking technique; III) evaluate functionally, the participation of projections from the dorsal hippocampus to the infralimbic cortex and nucleus accumbens in the reinstatement of context-induced ethanol seeking behavior, using the synaptic inhibition technique by optogenetics; and IV) identify as molecular changes between the synaptic contacts of the dorsal hippocampus projections to the infralimbic cortex and accumbens nuclei that are involved in the reinstatement of context-induced ethanol seeking behavior. (AU)