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Δ9-tetrahydrocannabinol (Δ9-THC) administration after neonatal exposure to phencyclidine potentiates schizophrenia-related behavioral phenotypes in mice.
Pharmacol Biochem Behav. 2017 08; 159:6-11.PB

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; 10mg/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, 5mg/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.

Authors+Show Affiliations

Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611, USA.Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611, USA.Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611, USA. Electronic address: KatherineYao2017@u.northwestern.edu.Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611, USA. Electronic address: h-meltzer@northwestern.edu.Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611, USA. Electronic address: jcsernan@nm.org.Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611, USA. Electronic address: h-dong@northwestern.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28648819

Citation

Rodríguez, Guadalupe, et al. "Δ9-tetrahydrocannabinol (Δ9-THC) Administration After Neonatal Exposure to Phencyclidine Potentiates Schizophrenia-related Behavioral Phenotypes in Mice." Pharmacology, Biochemistry, and Behavior, vol. 159, 2017, pp. 6-11.
Rodríguez G, Neugebauer NM, Yao KL, et al. Δ9-tetrahydrocannabinol (Δ9-THC) administration after neonatal exposure to phencyclidine potentiates schizophrenia-related behavioral phenotypes in mice. Pharmacol Biochem Behav. 2017;159:6-11.
Rodríguez, G., Neugebauer, N. M., Yao, K. L., Meltzer, H. Y., Csernansky, J. G., & Dong, H. (2017). Δ9-tetrahydrocannabinol (Δ9-THC) administration after neonatal exposure to phencyclidine potentiates schizophrenia-related behavioral phenotypes in mice. Pharmacology, Biochemistry, and Behavior, 159, 6-11. https://doi.org/10.1016/j.pbb.2017.06.010
Rodríguez G, et al. Δ9-tetrahydrocannabinol (Δ9-THC) Administration After Neonatal Exposure to Phencyclidine Potentiates Schizophrenia-related Behavioral Phenotypes in Mice. Pharmacol Biochem Behav. 2017;159:6-11. PubMed PMID: 28648819.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Δ9-tetrahydrocannabinol (Δ9-THC) administration after neonatal exposure to phencyclidine potentiates schizophrenia-related behavioral phenotypes in mice. AU - Rodríguez,Guadalupe, AU - Neugebauer,Nichole M, AU - Yao,Katherine Lan, AU - Meltzer,Herbert Y, AU - Csernansky,John G, AU - Dong,Hongxin, Y1 - 2017/06/23/ PY - 2017/02/21/received PY - 2017/06/15/revised PY - 2017/06/19/accepted PY - 2017/6/27/pubmed PY - 2018/5/22/medline PY - 2017/6/27/entrez KW - Behavior KW - Mice KW - Neonatal KW - PCP KW - Schizophrenia KW - Δ9-THC SP - 6 EP - 11 JF - Pharmacology, biochemistry, and behavior JO - Pharmacol Biochem Behav VL - 159 N2 - 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; 10mg/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, 5mg/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. SN - 1873-5177 UR - https://www.unboundmedicine.com/medline/citation/28648819/Δ9_tetrahydrocannabinol__Δ9_THC__administration_after_neonatal_exposure_to_phencyclidine_potentiates_schizophrenia_related_behavioral_phenotypes_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-3057(17)30121-1 DB - PRIME DP - Unbound Medicine ER -