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

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

doi:10.1111/ejn.14348

Cited by 30 publications

(17 citation statements)

References 68 publications

(96 reference statements)

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“…These results may reflect that the administration of these SCBs triggered impulsive behavior, which has been commonly observed in SCB users (Ozten et al, 2015;Altıntaş et al, 2019). Additionally, these impulsive effects of SCBs are supported by previous studies that cannabinoid receptors are responsible for impulsive behavior (Leffa et al, 2019;Wiskerke et al, 2012).…”

Section: Discussionsupporting

confidence: 76%

Abuse Potential of Synthetic Cannabinoids: AM-1248, CB-13, and PB-22

Jang

Lee

et al. 2021

Biomol Ther (Seoul)

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Currently, the expanding recreational use of synthetic cannabinoids (SCBs) threatens public health. SCBs produce psychoactive effects similar to those of tetrahydrocannabinol, the main component of cannabis, and additionally induce unexpected pharmacological side effects. SCBs are falsely advertised as legal and safe, but in reality, SCB abuse has been reported to cause acute intoxication and addictive disorders. However, because of the lack of scientific evidence to elucidate their dangerous pharmacological effects, SCBs are weakly regulated and continue to circulate in illegal drug markets. In the present study, the intravenous self-administration (IVSA) paradigm was used to evaluate the abuse potential of three SCBs (AM-1248, CB-13, and PB-22) in rats. All three SCBs maintained IVSA with a large number of infusions and active lever presses, demonstrating their reinforcing effects. The increase of active lever presses was particularly significant during the early IVSA sessions, indicating the reinforcementenhancing effects of the SCBs (AM-1248 and CB-13). The number of inactive lever presses was significantly higher in the SCB groups (AM-1248 and CB-13) than that in the vehicle group, indicating their impulsive effects. In summary, these results demonstrated that SCBs have distinct pharmacological properties and abuse potential.

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Section: Discussionsupporting

confidence: 76%

Abuse Potential of Synthetic Cannabinoids: AM-1248, CB-13, and PB-22

Jang

Lee

et al. 2021

Biomol Ther (Seoul)

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“…As regard to impulsivity, although an acute pretreatment with caffeine increased choices of large reward on SHR, a chronic treatment with caffeine increased the impulsive phenotype and decreased choices of large reward on SHR [25]. This discrepancy may be explained by previous studies performed on animal models of brain diseases, showing that while an acute treatment acts mainly on A1 receptors, a chronic treatment acts mainly on A2A receptors [32].…”

Section: Discussionmentioning

confidence: 98%

“…Leffa et al [25] focused on impulsive behavior to elucidate the neurobiology of ADHD. They treated SHR with caffeine, a non-selective adenosine receptor antagonist, to evaluate the modulating effects of the adenosine systems in a tolerance to delay of reward task.…”

Section: Impulsive Behaviormentioning

confidence: 99%

Effects of Caffeine Consumption on Attention Deficit Hyperactivity Disorder (ADHD) Treatment: A Systematic Review of Animal Studies

Vázquez¹,

Torre²,

Palomé³

et al. 2021

Preprint

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Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by a persistent pattern of inattention and/or hyperactivity-impulsivity. Neurobiologically, ADHD impairments arise from abnormalities in different circuits involving the prefrontal cortex. In face of high rates of diagnosis, alternative/complementary pharmacological therapeutic approaches for ADHD are needed. Although the number of publications that study the potential effects of caf-feine consumption on ADHD treatment have been accumulating over the last years, and caffeine has recently been used in ADHD research in the context of animal models, an updated evi-dence-based systematic review on the effects of caffeine on ADHD-like symptoms in animal stud-ies is missing. To provide insight and value at the preclinical level, a systematic review based on PRISMA guidelines was performed for all publications available up to September 1, 2021. Caffeine treatment increases attention, improves learning, memory and olfactory discrimination, without altering blood pressure and body weight. These results are supported at the neuronal level. Nonetheless, the implication of caffeine in modulating ADHD-like symptoms of hyperactivity and impulsivity is contradictory, raising discrepancies that require further clarification. Our results strengthen the hypothesis that caffeine cognitive effects found in animal models could be trans-lated to human ADHD, particularly during adolescence.

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“…An experiment carried out in SHR rats (an animal model reproducing some features of ADHD) evaluated the modulating effects of the cannabinoid system on impulsivity, using a delay reinforcement task and the administration of WIN55212-2 or AM251 (352). This study concluded that treatment with WIN55212-2 decreased whereas AM251 increased the choices of the large reward, suggesting that CB1r plays a relevant role in impulsive behavior.…”

Section: Animal Studiesmentioning

confidence: 98%