کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5515159 | 1541828 | 2017 | 6 صفحه PDF | دانلود رایگان |
- Neonatal PCP (P7) administration induces schizophrenia-like phenotypes.
- In this model, Î9-THC administration in young adults potentiates these phenotypes.
- Î9-THC or combined PCPÂ +Â Î9-THC decreases cortical CB1 receptor expression.
- PCP or combined PCPÂ +Â Î9-THC decreases cortical NR1 receptor expression.
The clinical onset of schizophrenia often coincides with cannabis use in adolescents and young adults. However, the neurobiological consequences of this co-morbidity are not well understood. In this study, we examined the effects of Î9-THC exposure during early adulthood on schizophrenia-related behaviors using a developmental mouse model of schizophrenia.Phencyclidine (PCP) or saline was administered once in neonatal mice (at P7; 10 mg/kg). In turn, Î9-THC or saline was administered sub-acutely later in life to cohorts of animals who had received either PCP or saline (P55-80, 5 mg/kg). Mice who were administered PCP alone displayed behavioral changes in the Morris water waze (MWM) and pre-pulse inhibition (PPI) task paradigm that were consistent with schizophrenia-related phenotypes, but not in the locomotor activity or novel object recognition (NOR) task paradigms. Mice who were administered PCP and then received Î9-THC later in life displayed behavioral changes in the locomotor activity paradigm (p < 0.001) that was consistent with a schizophrenia-related phenotype, as well as potentiated changes in the NOR (p < 0.01) and MWM (p < 0.05) paradigms as compared to mice that received PCP alone. Decreased cortical receptor expression of NMDA receptor 1 subunit (NR1) was observed in mice that received PCP and PCP + Î9-THC, while mice that received Î9-THC and PCP + Î9-THC displayed decreases in CB1 receptor expression. These findings suggest that administration of Î9-THC during the early adulthood can potentiate the development of schizophrenia-related behavioral phenotypes induced by neonatal exposure to PCP in mice.
Journal: Pharmacology Biochemistry and Behavior - Volume 159, August 2017, Pages 6-11