Immunohistochemical characterization of neuronal ensembles of amygdala involved in the context-induced reinstatement of ethanol seeking

• Grant number: 15/12002-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2015
• End date: December 31, 2016
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Fabio Cardoso Cruz
• Grantee: Letícia Camargo Tavares
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 13/24986-2 - The role of neuronal ensembles in context-induced reinstatement of ethanol seeking: pharmacogenetic, optogenetic and molecular investigation, AP.JP

Abstract

Learned associations play an important role in addiction. With repeated drug use, addicts learn to associate drug effects with stimuli or cues in the drug environment, such as drug paraphernalia, context, and people. Over time, these cues can promote drug craving and relapse. These drug-related cues are complex combinations of different stimuli that are recognized with a high degree of resolution. Thus, any neural mechanism capable of encoding these learned associations must have a comparably high degree of resolution. In this way, 1949, Donald Hebb hypothesized that learned associations are encoded by sparsely distributed patterns of synchronously activated neurons now called neuronal ensembles. We hypothesize that these strongly activated patterns of neurons, in amygdala form neuronal ensembles that encode learned associations between ethanol effects and environmental cues associated with these effects. One of the main problems for treating ethanol addiction is high rates of relapse to drug use. In human addicts, environmental stimuli associated with previous drug use can provoke relapse to drug use after prolonged abstinence. Many laboratories model drug relapse in rodents using a context-induced reinstatement procedure. In this procedure, rodents learn to associate particular environments or contexts with drug-taking. At a later time, investigators can re-expose rodents to the drug-associated context and examine its effects on relapse to drug seeking. We will characterize the different populations of neuronal ensembles in the amygdala that could be involved in the context-induced reinstatement of ethanol seeking. For this, we will train rats to self-administer ethanol in context A and extinguished lever pressing in a distinct context B. On test day, the context-induced reinstatement of ethanol seeking will be tested putting the rats back in the ethanol context (A). To characterise the neuronal ensembles involved in this behavior, at the end, we will perfuse the rats, the brains will be collected and immunohistochemistry essays will be used to phenotype and quantify the different populations of neurons in the amygdala. We hope that our preclinical procedure for context-induced reinstatement could find new targets for ethanol relapse treatment.