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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2018
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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 |
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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 |
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