期刊
EUROPEAN JOURNAL OF NEUROSCIENCE
卷 49, 期 12, 页码 1673-1683出版社
WILEY
DOI: 10.1111/ejn.14348
关键词
adenosine; ADHD; CB1 receptor; impulsivity; spontaneous hypertensive rats; Wistar-Kyoto rats
资金
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior
- Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro
- Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul
- Instituto Nacional de Ciencia e Tecnologia em Excitotoxicidade e Neuroprotecao
- CAPES-FCT [CENTRO-01-0145FEDER-000008: BrainHealth 20]
- FCT - Portugal [POCI-01-0145-FEDER-007440, PTDC/NEU-NMC/4154/20]
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 (WIN55212-2, WIN) or antagonist (AM251). 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 AM251 increased the choices of the large reward, selectively in SHR rats, indicating a CB1 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 CB1 receptors is applied to ADHD patients who consume coffee.
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