Δ9-tetrahydrocannabinol (Δ9-THC) administration after neonatal exposure to phencyclidine potentiates schizophrenia-related behavioral phenotypes in mice

Guadalupe Rodríguez, Nichole M Neugebauer, Katherine Lan Yao, Herbert Y Meltzer, John G Csernansky, Hongxin Dong*

*Corresponding author for this work

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

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 Δ9-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, Δ9-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 Δ9-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 + Δ9-THC, while mice that received Δ9-THC and PCP + Δ9-THC displayed decreases in CB1 receptor expression. These findings suggest that administration of Δ9-THC during the early adulthood can potentiate the development of schizophrenia-related behavioral phenotypes induced by neonatal exposure to PCP in mice.

Original languageEnglish (US)
Pages (from-to)6-11
Number of pages6
JournalPharmacology Biochemistry and Behavior
Volume159
DOIs
StatePublished - Aug 1 2017

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Keywords

  • Behavior
  • Mice
  • Neonatal
  • PCP
  • Schizophrenia
  • Δ9-THC

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

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