Impaired GAD1 expression in schizophrenia-related WISKET rat model with sex-dependent aggressive behavior and motivational deficit.
Genes Brain Behav
; 18(4): e12507, 2019 04.
Article
en En
| MEDLINE
| ID: mdl-30051606
ABSTRACT
After peri-adolescence isolation rearing (IS) and subchronic ketamine (KET) treatment, adult, selectively bred Wistar rats (named WISKET) mimic abnormal behaviors reminiscent of human schizophrenia, including reduced prepulse-inhibition of startle reflex, disturbances in cognition, locomotor activity and thermoregulation, decreased pain sensitivity and electrophysiological alterations. To further validate our WISKET rat line, regarding its translational utility in schizophrenia research, we examined their social behavior and introduced a short and simple holeboard (HB)-like test to investigate their motivational deficit that predicts the cognitive disturbance. Sex-dependent alterations in schizophrenia may yield important insights into its etiology; thus, male and female WISKET rats were also investigated and compared with their naive Wistar counterparts. Considering the contribution of the hippocampal and cortical GABAergic inhibitory circuitry in these behavioral alterations, molecular-biology studies were also performed regarding the GAD1 gene products. Impaired social activity with increased aggression, stress-related behavior, active social withdrawal, motivation deficit and decreased exploration were observed, especially in male WISKET rats, compared with Wistar ones and their corresponding females. These alterations were accompanied by sex-dependent alterations regarding GAD67 mRNA and protein expression in the prefrontal cortex and hippocampus. In conclusion, the WISKET animals are valuable tools for animal-based preclinical drug discovery studies for predictive screening of novel compounds improving negative symptoms with potential antipsychotic efficacy.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Esquizofrenia
/
Agresión
/
Glutamato Descarboxilasa
/
Motivación
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Genes Brain Behav
Asunto de la revista:
CIENCIAS DO COMPORTAMENTO
/
GENETICA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Hungria