LiCl Pretreatment Ameliorates Adolescent Methamphetamine Exposure-Induced Long-Term Alterations in Behavior and Hippocampal Ultrastructure in Adulthood in Mice.
Int J Neuropsychopharmacol
; 22(4): 303-316, 2019 04 01.
Article
em En
| MEDLINE
| ID: mdl-30649326
ABSTRACT
BACKGROUND:
Adolescent methamphetamine exposure causes a broad range of neurobiological deficits in adulthood. Glycogen synthase kinase-3ß is involved in various cognitive and behavioral processes associated with methamphetamine exposure. This study aims to investigate the protective effects of the glycogen synthase kinase-3ß inhibitor lithium chloride on adolescent methamphetamine exposure-induced long-term alterations in emotion, cognition, behavior, and molecule and hippocampal ultrastructure in adulthood.METHODS:
A behavioral test battery was used to investigate the protective effects of lithium chloride on adolescent methamphetamine exposure-induced long-term emotional, cognitive, and behavioral impairments in mice. Western blotting and immunohistochemistry were used to detect glycogen synthase kinase-3ß activity levels in the medial prefrontal cortex and dorsal hippocampus. Electron microscopy was used to analyze changes in synaptic ultrastructure in the dorsal hippocampus. Locomotor sensitization with a methamphetamine (1 mg/kg) challenge was examined 80 days after adolescent methamphetamine exposure.RESULTS:
Adolescent methamphetamine exposure induced long-term alterations in locomotor activity, novel spatial exploration, and social recognition memory; increases in glycogen synthase kinase-3ß activity in dorsal hippocampus; and decreases in excitatory synapse density and postsynaptic density thickness in CA1. These changes were ameliorated by lithium chloride pretreatment. Adolescent methamphetamine exposure-induced working memory deficits in Y-maze spontaneous alternation test and anxiety-like behavior in elevated-plus maze test spontaneously recovered after long-term methamphetamine abstinence. No significant locomotor sensitization was observed after long-term methamphetamine abstinence.CONCLUSIONS:
Hyperactive glycogen synthase kinase-3ß contributes to adolescent chronic methamphetamine exposure-induced behavioral and hippocampal impairments in adulthood. Our results suggest glycogen synthase kinase-3ß may be a potential target for the treatment of deficits in adulthood associated with adolescent methamphetamine abuse.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Comportamento Animal
/
Cloreto de Lítio
/
Inibidores Enzimáticos
/
Disfunção Cognitiva
/
Glicogênio Sintase Quinase 3 beta
/
Hipocampo
/
Estimulantes do Sistema Nervoso Central
/
Metanfetamina
Limite:
Animals
Idioma:
En
Revista:
Int J Neuropsychopharmacol
Assunto da revista:
NEUROLOGIA
/
PSICOFARMACOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article