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

Autor: Daniel J. Lodge, David Aguilar, Andrea Giuffrida
Rok vydání: 2018
Předmět:
medicine.medical_specialty
Psychosis
medicine.medical_treatment
Hippocampus
Regular Research Articles
Rats
Sprague-Dawley
WIN55
212-2
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Interneurons
Internal medicine
parvalbumin
Synthetic cannabinoids
medicine
Animals
Pharmacology (medical)
Amphetamine
Pharmacology
Methylazoxymethanol acetate
Behavior
Animal
Cannabinoids
business.industry
Dopaminergic Neurons
Age Factors
methylazoxymethanol acetate
URB597
electrophysiology
medicine.disease
Endocannabinoid system
Rats
Up-Regulation
3. Good health
030227 psychiatry
Disease Models
Animal
Psychiatry and Mental health
Endocrinology
chemistry
Schizophrenia
Central Nervous System Stimulants
Disease Susceptibility
Cannabinoid
business
030217 neurology & neurosurgery
Endocannabinoids
medicine.drug
Zdroj: International Journal of Neuropsychopharmacology
ISSN: 1469-5111
1461-1457
DOI: 10.1093/ijnp/pyy003
Popis: 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.
Databáze: OpenAIRE
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