S-111 | Perinatal Protein Restriction Facilitates Anxiety- and Anhedonia-like Behaviors in Rats During Cocaine Withdrawal

Neurochemistry and Neuropharmacology
Author: Maria Cecilia Gutierrez | Email: cecilia.gutierrez@unc.edu.ar

Maria Cecilia Gutierrez^1°2°, Maria Cecilia Perondi^1°, Luis Manzanelli^1°,  Analia Valdomero^1°2°

^1° Departamento de Farmacología Otto Orsingher, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba
^2° IFEC (CONICET).

Previously, we showed that perinatal protein restriction increases the rewarding effects of cocaine, and facilitates the reinstatement of extinguished conditioned place preference. Relapse into substance use during abstinence is often associated with withdrawal symptoms such as anxiety and depressive-like behavior. This study aimed to investigate whether early malnutrition facilitates these behaviors in cocaine-abstinent adult animals. To achieve this, different groups of male adult rats, subjected to a perinatal protein restriction schedule (PR-rats) and normoprotein diet (NP-rats), received a daily i.p. injection of either saline (1 ml/kg) or cocaine (5 or 10 mg/kg) for 7 days. After 4 and 7 days of withdrawal (WD), we evaluated anxiety and anhedonia-like behavior in the elevated plus maze (EPM) and sucrose preference test (SPT), respectively. The results showed that PR-rats spent less time in the open arms of the EPM on WD 4 and 7 with both doses of cocaine, indicating anxiety-like behavior. This effect was observed in NP-rats only with the higher dose of cocaine on WD7. In the SPT, early malnutrition reduced sucrose preference on both WD 4 and 7, regardless of the treatment. These findings demonstrate that nutritional injury facilitates anxiety-like behavior and induces anhedonia, a depression-related symptom during cocaine abstinence. This suggests that early malnutrition may contribute to relapse into substance use during withdrawal by facilitating these behaviors.