PMID- 32032697
OWN - NLM
STAT- MEDLINE
DCOM- 20210428
LR  - 20210428
IS  - 1878-4216 (Electronic)
IS  - 0278-5846 (Print)
IS  - 0278-5846 (Linking)
VI  - 100
DP  - 2020 Jun 8
TI  - Prenatal THC exposure raises kynurenic acid levels in the prefrontal cortex of 
      adult rats.
PG  - 109883
LID - S0278-5846(20)30001-4 [pii]
LID - 10.1016/j.pnpbp.2020.109883 [doi]
AB  - Cannabis remains one of the most widely used illicit drugs during pregnancy. The 
      main psychoactive component of marijuana (Delta(9)-tetrahydrocannabinol, THC) is 
      correlated with untoward physiological effects in the offspring. Neurobehavioral 
      and cognitive impairments have been reported in longitudinal studies on children 
      and adolescents prenatally exposed to marijuana, and a link to psychiatric 
      disorders has been proposed. Interestingly, the deleterious effects of prenatal 
      cannabis use are similar to those observed in adult rats prenatally exposed to 
      (L)-kynurenine, the direct bioprecursor of the neuroactive metabolite kynurenic 
      acid (KYNA). We therefore investigated whether alterations in KYNA levels in the 
      rat brain might play a role in the long-term consequences of prenatal cannabinoid 
      exposure. Pregnant Wistar rats were treated daily with THC [5 mg/kg, p.o.] from 
      gestational day (GD)5 through GD20. Using in vivo microdialysis in the medial 
      prefrontal cortex, adult animals were then used to determine the extracellular 
      levels of KYNA and glutamate. Compared to controls, extracellular basal KYNA 
      levels were higher, and basal glutamate levels were lower, in prenatally 
      THC-exposed rats. These rats also showed abnormal short-term memory. Following an 
      additional acute challenge with a low dose of kynurenine (5 mg/kg i.p.) in 
      adulthood, the increase in extracellular KYNA levels in the mPFC was more 
      pronounced in in prenatally THC-exposed rats. These effects could be causally 
      related to the cognitive dysfunction seen in prenatally THC-exposed rats. In the 
      translational realm, these experiments raise the prospect of prevention of KYNA 
      neosynthesis as a promising novel approach to combat some of the detrimental 
      long-term effects of prenatal cannabis use.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Beggiato, Sarah
AU  - Beggiato S
AD  - Department of Life Sciences and Biotechnologies, University of Ferrara, Ferrara, 
      Italy; Department of Medical, Oral and Biotechnological Sciences, University of 
      Chieti-Pescara, Chieti, Italy. Electronic address: bggsrh@unife.it.
FAU - Ieraci, Alessandro
AU  - Ieraci A
AD  - Department of Pharmaceutical Sciences, University of Milan, Milano, Italy.
FAU - Tomasini, Maria Cristina
AU  - Tomasini MC
AD  - Department of Life Sciences and Biotechnologies, University of Ferrara, Ferrara, 
      Italy.
FAU - Schwarcz, Robert
AU  - Schwarcz R
AD  - Maryland Psychiatric Research Center, Department of Psychiatry, University of 
      Maryland School of Medicine, Baltimore, MD, USA.
FAU - Ferraro, Luca
AU  - Ferraro L
AD  - Department of Life Sciences and Biotechnologies, University of Ferrara, Ferrara, 
      Italy; Laboratory for the Technology of Advanced Therapies (LTTA Centre), 
      University of Ferrara, Ferrara, Italy.
LA  - eng
GR  - P50 MH103222/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200204
PL  - England
TA  - Prog Neuropsychopharmacol Biol Psychiatry
JT  - Progress in neuro-psychopharmacology & biological psychiatry
JID - 8211617
RN  - 0 (Biomarkers)
RN  - 0 (Hallucinogens)
RN  - 7J8897W37S (Dronabinol)
RN  - H030S2S85J (Kynurenic Acid)
SB  - IM
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Dronabinol/administration & dosage/*toxicity
MH  - Female
MH  - Hallucinogens/administration & dosage/toxicity
MH  - Kynurenic Acid/*metabolism
MH  - Male
MH  - Memory, Short-Term/drug effects/physiology
MH  - Prefrontal Cortex/*drug effects/*metabolism
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/*chemically induced/*metabolism/psychology
MH  - Rats
MH  - Rats, Wistar
PMC - PMC7260707
MID - NIHMS1591531
OTO - NOTNLM
OT  - Cognition
OT  - Kynurenic acid
OT  - Kynurenine
OT  - Prefrontal cortex
OT  - Prenatal
OT  - THC
COIS- Declaration of Competing Interest The authors declare no conflict of interest.
EDAT- 2020/02/08 06:00
MHDA- 2021/04/29 06:00
PMCR- 2020/06/08
CRDT- 2020/02/08 06:00
PHST- 2020/01/02 00:00 [received]
PHST- 2020/01/31 00:00 [revised]
PHST- 2020/02/03 00:00 [accepted]
PHST- 2020/02/08 06:00 [pubmed]
PHST- 2021/04/29 06:00 [medline]
PHST- 2020/02/08 06:00 [entrez]
PHST- 2020/06/08 00:00 [pmc-release]
AID - S0278-5846(20)30001-4 [pii]
AID - 10.1016/j.pnpbp.2020.109883 [doi]
PST - ppublish
SO  - Prog Neuropsychopharmacol Biol Psychiatry. 2020 Jun 8;100:109883. doi: 
      10.1016/j.pnpbp.2020.109883. Epub 2020 Feb 4.