Cargando…

Adolescent Synthetic Cannabinoid Exposure Produces Enduring Changes in Dopamine Neuron Activity in a Rodent Model of Schizophrenia Susceptibility

BACKGROUND: Epidemiological studies recognize cannabis intake as a risk factor for schizophrenia, yet the majority of adolescents who use marijuana do not develop psychosis. Similarly, the abuse of synthetic cannabinoids poses a risk for psychosis. For these reasons, it is imperative to understand t...

Descripción completa

Detalles Bibliográficos
Autores principales: Aguilar, David D, Giuffrida, Andrea, Lodge, Daniel J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5887672/
https://www.ncbi.nlm.nih.gov/pubmed/29329382
http://dx.doi.org/10.1093/ijnp/pyy003
_version_ 1783312356011409408
author Aguilar, David D
Giuffrida, Andrea
Lodge, Daniel J
author_facet Aguilar, David D
Giuffrida, Andrea
Lodge, Daniel J
author_sort Aguilar, David D
collection PubMed
description BACKGROUND: Epidemiological studies recognize cannabis intake as a risk factor for schizophrenia, yet the majority of adolescents who use marijuana do not develop psychosis. Similarly, the abuse of synthetic cannabinoids poses a risk for psychosis. For these reasons, it is imperative to understand the effects of adolescent cannabinoid exposure in susceptible individuals. METHODS: We recently developed a novel rodent model of schizophrenia susceptibility, the F2 methylazoxymethanol acetate rat, where only a proportion (~40%) of rats display a schizophrenia-like phenotype. Using this model, we examined the effects of adolescent synthetic cannabinoid exposure (0.2 mg/kg WIN55, 212-2, i.p.) or adolescent endocannabinoid upregulation (0.3 mg/kg URB597, i.p.) on dopamine neuron activity and amphetamine sensitivity in adulthood. RESULTS: Adolescent synthetic cannabinoid exposure significantly increased the proportion of susceptible rats displaying a schizophrenia-like hyperdopaminergic phenotype after puberty without producing any observable alterations in control rats. Furthermore, this acquired phenotype appears to correspond with alterations in parvalbumin interneuron function within the hippocampus. Endocannabinoid upregulation during adolescence also increased the proportion of susceptible rats developing an increase in dopamine neuron activity; however, it did not alter the behavioral response to amphetamine, further emphasizing differences between exogenous and endogenous cannabinoids. CONCLUSIONS: Taken together, these studies provide experimental evidence that adolescent synthetic cannabinoid exposure may contribute to psychosis in susceptible individuals.
format Online
Article
Text
id pubmed-5887672
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-58876722018-04-11 Adolescent Synthetic Cannabinoid Exposure Produces Enduring Changes in Dopamine Neuron Activity in a Rodent Model of Schizophrenia Susceptibility Aguilar, David D Giuffrida, Andrea Lodge, Daniel J Int J Neuropsychopharmacol Regular Research Articles BACKGROUND: Epidemiological studies recognize cannabis intake as a risk factor for schizophrenia, yet the majority of adolescents who use marijuana do not develop psychosis. Similarly, the abuse of synthetic cannabinoids poses a risk for psychosis. For these reasons, it is imperative to understand the effects of adolescent cannabinoid exposure in susceptible individuals. METHODS: We recently developed a novel rodent model of schizophrenia susceptibility, the F2 methylazoxymethanol acetate rat, where only a proportion (~40%) of rats display a schizophrenia-like phenotype. Using this model, we examined the effects of adolescent synthetic cannabinoid exposure (0.2 mg/kg WIN55, 212-2, i.p.) or adolescent endocannabinoid upregulation (0.3 mg/kg URB597, i.p.) on dopamine neuron activity and amphetamine sensitivity in adulthood. RESULTS: Adolescent synthetic cannabinoid exposure significantly increased the proportion of susceptible rats displaying a schizophrenia-like hyperdopaminergic phenotype after puberty without producing any observable alterations in control rats. Furthermore, this acquired phenotype appears to correspond with alterations in parvalbumin interneuron function within the hippocampus. Endocannabinoid upregulation during adolescence also increased the proportion of susceptible rats developing an increase in dopamine neuron activity; however, it did not alter the behavioral response to amphetamine, further emphasizing differences between exogenous and endogenous cannabinoids. CONCLUSIONS: Taken together, these studies provide experimental evidence that adolescent synthetic cannabinoid exposure may contribute to psychosis in susceptible individuals. Oxford University Press 2018-01-10 /pmc/articles/PMC5887672/ /pubmed/29329382 http://dx.doi.org/10.1093/ijnp/pyy003 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of CINP. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Regular Research Articles
Aguilar, David D
Giuffrida, Andrea
Lodge, Daniel J
Adolescent Synthetic Cannabinoid Exposure Produces Enduring Changes in Dopamine Neuron Activity in a Rodent Model of Schizophrenia Susceptibility
title Adolescent Synthetic Cannabinoid Exposure Produces Enduring Changes in Dopamine Neuron Activity in a Rodent Model of Schizophrenia Susceptibility
title_full Adolescent Synthetic Cannabinoid Exposure Produces Enduring Changes in Dopamine Neuron Activity in a Rodent Model of Schizophrenia Susceptibility
title_fullStr Adolescent Synthetic Cannabinoid Exposure Produces Enduring Changes in Dopamine Neuron Activity in a Rodent Model of Schizophrenia Susceptibility
title_full_unstemmed Adolescent Synthetic Cannabinoid Exposure Produces Enduring Changes in Dopamine Neuron Activity in a Rodent Model of Schizophrenia Susceptibility
title_short Adolescent Synthetic Cannabinoid Exposure Produces Enduring Changes in Dopamine Neuron Activity in a Rodent Model of Schizophrenia Susceptibility
title_sort adolescent synthetic cannabinoid exposure produces enduring changes in dopamine neuron activity in a rodent model of schizophrenia susceptibility
topic Regular Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5887672/
https://www.ncbi.nlm.nih.gov/pubmed/29329382
http://dx.doi.org/10.1093/ijnp/pyy003
work_keys_str_mv AT aguilardavidd adolescentsyntheticcannabinoidexposureproducesenduringchangesindopamineneuronactivityinarodentmodelofschizophreniasusceptibility
AT giuffridaandrea adolescentsyntheticcannabinoidexposureproducesenduringchangesindopamineneuronactivityinarodentmodelofschizophreniasusceptibility
AT lodgedanielj adolescentsyntheticcannabinoidexposureproducesenduringchangesindopamineneuronactivityinarodentmodelofschizophreniasusceptibility