Adolescent cocaine induced persistent negative affect in female rats exposed to early-life stress

Rationale The combination of several risk factors (sex, a prior underlying psychiatric condition, or early drug initiation) could induce the emergence of negative affect during cocaine abstinence and increase the risk of developing addiction. However, most prior preclinical studies have been centere...

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Detalhes bibliográficos
Autores: Bis-Humbert, Cristian, García-Fuster, M Julia
Formato: artículo
Fecha de publicación:2021
País:España
Recursos:Conselleria de Salut i Consum del Govern de les Illes Balears
Repositorio:Docusalut
Idioma:inglés
OAI Identifier:oai:docusalut.com:20.500.13003/19425
Acesso em linha:https://hdl.handle.net/20.500.13003/19425
Access Level:acceso abierto
Palavra-chave:Male
Cocaine
Cocaine-Related Disorders
Female
Rats
Animals
Maternal Deprivation
Rats, Sprague-Dawley
Adverse Childhood Experiences
Experiencias Adversas de la Infancia
Animales
Ratas
Ratas Sprague-Dawley
Privación Materna
Femenino
Cocaína
Trastornos Relacionados con Cocaína
Masculino
Adolescence
Maternal deprivation
Negative affect
Rat
Descrição
Resumo:Rationale The combination of several risk factors (sex, a prior underlying psychiatric condition, or early drug initiation) could induce the emergence of negative affect during cocaine abstinence and increase the risk of developing addiction. However, most prior preclinical studies have been centered in male rodents, traditionally excluding females from these analyses. Objectives To ascertain the behavioral and neurochemical consequences of adolescent cocaine exposure when the combination of several risk factors is present (female, early-life stress). Methods Whole litters of Sprague-Dawley rats were exposed to maternal deprivation for 24 h on postnatal day (PND) 9. Cocaine was administered in adolescence (15 mg/kg/day, i.p., PND 33-39). Negative affect was assessed by several behavioral tests (forced swim, open field, novelty-suppressed feeding, sucrose preference). Hippocampal cell fate markers were evaluated by western blot (FADD, Bax, cytochrome c) or immunohistochemistry (Ki-67; cell proliferation). Results Maternal deprivation is a suitable model of psychiatric vulnerability in which to study the impact of adolescent cocaine in female rats. While adolescent cocaine did not alter affective-like behavior during adolescence, a pro-depressive-like state emerged during adulthood, exclusively in rats re-exposed to cocaine during abstinence. FADD regulation by cocaine in early-life stressed female rats might contribute to certain hippocampal neuroadaptations with some significance to the observed induced negative affect. Conclusions Adolescent cocaine induced persistent negative affect in female rats exposed to early-life stress, highlighting the risk of early drug initiation during adolescence for the emergence of negative reinforcement during abstinence likely driving cocaine addiction vulnerability, also in female rats.