Caffeine and cannabinoid receptors modulate impulsive behavior in an animal model of attentional deficit and hyperactivity disorder

Leffa, Douglas T.; Ferreira, Samira G.; Machado, Nuno J.; Souza, Carolina M.; Rosa, Fernanda da; de Carvalho, Cristiane; Kincheski, Grasielle C.; Takahashi, Reinaldo N.; Porciúncula, Lisiane O.; Souza, Diogo O.; Cunha, Rodrigo A.; Pandolfo, Pablo

doi:10.1111/ejn.14348

Title: Caffeine and cannabinoid receptors modulate impulsive behavior in an animal model of attentional deficit and hyperactivity disorder

Journal Article · 07 February 2019 · European Journal of Neuroscience

DOI: https://doi.org/10.1111/ejn.14348 · OSTI ID:1494158

Leffa, Douglas T. ^[1]; Ferreira, Samira G. ^[2]; Machado, Nuno J. ^[2]; Souza, Carolina M. ^[2]; Rosa, Fernanda da ^[2]; de Carvalho, Cristiane ^[3]; Kincheski, Grasielle C. ^[4]; Takahashi, Reinaldo N. ^[3]; Porciúncula, Lisiane O. ^[1]; Souza, Diogo O. ^[1]; Cunha, Rodrigo A. ^[5]; Pandolfo, Pablo ^[6]

Department of Biochemistry Universidade Federal do Rio Grande do Sul Porto Alegre Brazil
CNC‐Center for Neuroscience and Cell Biology University of Coimbra Coimbra Portugal
Department of Pharmacology Universidade Federal de Santa Catarina Florianópolis Brazil
Institute of Medical Biochemistry Leopoldo de Meis Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil
CNC‐Center for Neuroscience and Cell Biology University of Coimbra Coimbra Portugal, Faculty of Medicine University of Coimbra Coimbra Portugal
Department of Neurobiology Universidade Federal Fluminense Niterói Brazil

Abstract Attention deficit and hyperactivity disorder ( ADHD ) is characterized by impaired levels of hyperactivity, impulsivity, and inattention. Adenosine and endocannabinoid systems tightly interact in the modulation of dopamine signaling, involved in the neurobiology of ADHD . In this study, we evaluated the modulating effects of the cannabinoid and adenosine systems in a tolerance to delay of reward task using the most widely used animal model of ADHD . Spontaneous Hypertensive Rats ( SHR ) and Wistar–Kyoto rats were treated chronically or acutely with caffeine, a non‐selective adenosine receptor antagonist, or acutely with a cannabinoid agonist ( WIN 55212‐2, WIN ) or antagonist ( AM 251). Subsequently, animals were tested in the tolerance to delay of reward task, in which they had to choose between a small, but immediate, or a large, but delayed, reward. Treatment with WIN decreased, whereas treatment with AM 251 increased the choices of the large reward, selectively in SHR rats, indicating a CB ₁ receptor‐mediated increase in impulsive behavior. An acute pre‐treatment with caffeine blocked WIN effects. Conversely, a chronic treatment with caffeine increased the impulsive phenotype and potentiated the WIN effects. The results indicate that both cannabinoid and adenosine receptors modulate impulsive behavior in SHR : the antagonism of cannabinoid receptors might be effective in reducing impulsive symptoms present in ADHD ; in addition, caffeine showed the opposite effects on impulsive behavior depending on the length of treatment. These observations are of particular importance to consider when therapeutic manipulation of CB 1 receptors is applied to ADHD patients who consume coffee.

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Sponsoring Organization:: USDOE

OSTI ID:: 1494158

Journal Information:: European Journal of Neuroscience, Journal Name: European Journal of Neuroscience Journal Issue: 12 Vol. 49; ISSN 0953-816X

Publisher:: Wiley-BlackwellCopyright Statement

Country of Publication:: Country unknown/Code not available

Language:: English

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