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Cited by 68Cannabis and Cannabinoid ResearchSchizophrenia research and treatmentNeurotransmitter Receptor Influence on Behavior

Effects of Pubertal Cannabinoid Administration on Attentional Set-Shifting and Dopaminergic Hyper-Responsivity in a Developmental Disruption Model of Schizophrenia

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Gomes, Felipe V., Guimarães, Francisco S., Grace, Anthony A.·2015·International Journal of Neuropsychopharmacology
DOI 10.1093/ijnp/pyu018PMC PMC4368886
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Abstract

BACKGROUND: Adolescent exposure to cannabinoids in vulnerable individuals is proposed to be a risk factor for psychiatric conditions later in life, particularly schizophrenia. Evidence from studies in animals has indicated that a combination of repeated pubertal cannabinoid administration with either neonatal prefrontocortical lesion, isolation rearing, or chronic NMDA receptor antagonism administration induces enhanced schizophrenia-like behavioral disruptions. The effects of adolescent exposure to CB1 receptor agonists, however, have not been tested in a developmental disruption model of schizophrenia. METHODS: This was tested in the methylazoxymethanol (MAM) model, in which repeated treatment with the synthetic cannabinoid agonist WIN 55,212-2 (WIN; 1.2mg/kg) was extended over 25 days throughout puberty (postnatal days 40-65) in control and MAM rats. The rats received 20 injections, which were delivered irregularly to mimic the human condition. Adult rats were tested for attentional set-shifting task and locomotor response to amphetamine, which was compared with in vivo recording from ventral tegmental area (VTA) dopamine (DA) neurons. RESULTS: MAM-treated rats showed impairment in the attentional set-shifting task, augmented locomotor response to amphetamine administration, and an increased number of spontaneously active DA neurons in the VTA. Interestingly, pubertal WIN treatment in normal animals induced similar changes at adulthood as those observed in MAM-treated rats, supporting the notion that adolescence exposure to cannabinoids may represent a risk factor for developing schizophrenia-like signs at adulthood. However, contrary to expectations, pubertal WIN administration did not exacerbate the behavioral and electrophysiological changes in MAM-treated rats beyond that observed in WIN-treated saline rats (Sal). Indeed, WIN treatment actually attenuated the locomotor response to amphetamine in MAM rats without impacting DA neuron activity states. CONCLUSIONS: Taken together, the present results indicate that the impact of cannabinoids during puberty/adolescence on schizophrenia models is more complex than may be predicted.

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Cited by

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Authors
Gomes, F. V., Guimarães, F. S., & Grace, A. A.
Affiliations
University of Pittsburgh (US)
Corresponding author
Gomes, Felipe V.
ORCID
Venue
International Journal of Neuropsychopharmacology
Publisher
Oxford University Press (OUP)
Published
2015-01-13
Volume
18
Issue
2
ISSN
  • 1461-1457 (ISSN-L)
  • 1469-5111
DOI
10.1093/ijnp/pyu018
PMC
PMC4368886
OpenAlex
W2114222088
Cited by
68
References
7
Citations by year
2025: 2 · 2024: 7 · 2023: 8 · 2022: 5 · 2021: 10 · 2020: 10 · 2019: 3 · 2018: 6 · 2017: 10 · 2016: 3 · 2015: 4
FWCI
5.53
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • The International Journal of Neuropsychopharmacology (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (2010/17343-0)
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico
  • National Institutes of Health (2r01mh057440-26a1)
  • U.S. Public Health Service (MH57440, USPHS MH57440)
  • National Institute of Mental Health (MH-57440, R01-MH057440, R37MH057440)
  • Division of Graduate Education
Topics
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
adolescent cannabis exposure, schizophrenia risk, methylazoxymethanol, WIN 55,212-2, CB1 receptor agonists, set-shifting, ventral tegmental area dopamine neurons, schizophrenia risk factors
MeSH terms
Amphetamine, Central Nervous System Stimulants, Animals, Attention, Cannabinoids, Disease Models, Animal, Female, Male, Methylazoxymethanol Acetate, Morpholines, Motor Activity, Naphthalenes, Neuropsychological Tests, Pregnancy, Prenatal Exposure Delayed Effects, Schizophrenia, Schizophrenic Psychology, Rats, Sprague-Dawley, Ventral Tegmental Area, Benzoxazines, Executive Function, Dopaminergic Neurons

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