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

作者：Aguilar David D^*; Giuffrida Andrea; Lodge Daniel J

来源：International Journal of Neuropsychopharmacology, 2018, 21(4): 393-403.

DOI：10.1093/ijnp/pyy003

• URB597
• WIN55,212-1
• methylazoxymethanol acetate
• electrophysiology
• parvalbumin

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 (similar to 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.

• 出版日期2018-4