Caffeine improves attention deficit in neonatal 6-OHDA lesioned rats, an animal model of attention deficit hyperactivity disorder (ADHD)

Caballero, Miguel; Núñez, Fabiana; Ahern, S; Cuffi, M.L.; Carbonell, L.; Sánchez, Sílvia; Fernández-Dueñas, Víctor; Ciruela, Francisco

doi:10.1016/j.neulet.2011.02.050

Cited by 32 publications

(25 citation statements)

References 29 publications

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“…Adenosine A 1 receptors and dopamine D 1 receptors, as well as adenosine A 2A and dopamine D 2 receptors, have antagonizing actions (Ferré et al., ; Fuxe, Ferré, Zoli, & Agnati, ), which involve the formation of heteromers of adenosine and dopamine receptors (Ciruela et al., ). Caffeine, a non‐selective antagonist of A 1 and A 2A receptors, improves attention and short‐term memory in an animal model of ADHD (Caballero et al., ; Pandolfo, Machado, Köfalvi, Takahashi, & Cunha, ). This prompts the suggestion that caffeine might have clinical benefits in ADHD patients by increasing dopaminergic neurotransmission (Ioannidis, Chamberlain, & Muller, ).…”

Section: Introductionmentioning

confidence: 99%

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

Leffa

Ferreira

Machado

et al. 2019

Eur J of Neuroscience

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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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Section: Introductionmentioning

confidence: 99%

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

Leffa

Ferreira

Machado

et al. 2019

Eur J of Neuroscience

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“…Both drugs produce subjective effects that are characteristic of psychomotor stimulants (Benwell and Balfour, 1992; Lau and Falk, 1995); however, these effects are moderate in comparison to the more prototypical stimulants such as amphetamine (Antoniou et al, 1998; Boye et al, 2001). Both drugs increase attention and vigilance (Brunye et al, 2010; Caballero et al, 2011; Vangkilde et al, 2011) and neither of the drugs is a strong intoxicant – intoxicating effects are limited to high dosages and are often described as aversive (Perkins et al, 2003; Sigmon and Griffiths, 2011). Both drugs are reinforcers in humans (Griffiths and Chausmer, 2000; Perkins et al, 2004), however, their abuse liability has been questioned, which may stem from another shared characteristic of nicotine and caffeine: the difficulty of measuring their reinforcing effects in non-human subjects (Atkinson and Enslen, 1976; Hoffmeister and Wuttke, 1973; Myers and Izbicki, 2006).…”

Section: Introductionmentioning

confidence: 99%

Caffeine increases the motivation to obtain non-drug reinforcers in rats

Sheppard

Gross

Pavelka

et al. 2012

Drug and Alcohol Dependence

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BACKGROUND Caffeine is widely considered to be a reinforcer in humans, but this effect is difficult to measure in non-human animals. We hypothesized that caffeine may have dual reinforcing effects comparable to nicotine - limited primary reinforcing effects, but potent reinforcement enhancing effects. The present studies tested this hypothesis by investigating the effect of caffeine on responding for non-drug rewards. METHODS In two experiments, rats were shaped to respond on a progressive ratio (PR) schedule for sucrose solution (20% w/v; Experiment 1) or a fixed ratio 2 (FR2) schedule for a moderately reinforcing visual stimulus (VS; Experiment 2). Pretreatment with various doses of caffeine (0–50 mg/kg, intraperitoneal injection) were administered prior to tests over successive week days (M-F). In Experiment 1, acute administration of low-moderate caffeine doses (6.25–25 mg/kg) increased responding for sucrose under the PR schedule. This effect of caffeine declined over the initial 15 test days. In Experiment 2, only acute pretreatment with 12.5 mg/kg caffeine increased responding for the visual stimulus and complete tolerance to this effect of caffeine was observed over the 15 days of testing. In follow up tests we found that abstinence periods of 4 and 8 days resulted in incomplete recovery of the enhancing effects of caffeine. CONCLUSION The findings suggest that caffeine enhances the reinforcing effects of non-drug stimuli, but that the pharmacological profile of these effects may differ from other psychomotor stimulants.

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“…Many reports have shown hyperactivity disorder in 6-OHDA-lesioned rats (Heffner and Seiden 1982;Davids et al 2002;Caballero et al 2011). Heffner and Seiden (1982) reported that rats given 6-OHDA treatment displayed more than 6-fold increase in locomotor hyperactivity compared with controls on postnasal day 46.…”

Section: Discussionmentioning

confidence: 99%

“…ADHD is a common behavioral illness characterized by persistent symptoms of inattention, hyperactivity, and impulsivity. Although 6-hydroxydopamine (6-OHDA)lesioned rats have been used as an animal model of ADHD (Heffner and Seiden 1982;Davids et al 2002;Caballero et al 2011), it is expected that the underlying etiologies for ADHD are elucidated, and that a novel treatment for ADHD is developed.…”

Section: Introductionmentioning

confidence: 99%

Sleep Disturbance and Hyperactivity Detected by Actigraphy in Rats with Allergic Rhinitis or Attention-Deficit Hyperactivity Disorder

Suzuki

Nakayama

Ando

et al. 2018

Tohoku J. Exp. Med.

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Actigraphy is an easy and noninvasive method used to monitor human ultradian cycles. However, to our knowledge, it has been not applied to experiments with rodents. Therefore, using actigraphy, we assessed the ultradian cycles and behavior of rats. Rats with or without allergic rhinitis wore an actigraphy device, and triaxial acceleration was recorded. allergic rhinitis rats than in control rats (p < 0.01), suggesting the presence of difficulty with sleep induction in rats with allergic rhinitis. The counts from 18:00 to 20:00 were also significantly higher in allergic rhinitis rats than in control rats (p < 0.05), suggesting the presence of early awakening in rats with allergic rhinitis. Moreover, the counts were significantly higher in allergic rhinitis rats than in control rats from 20:00 to 8:00. These results suggest that rats with allergic rhinitis experienced hyperactivity disorder during the daytime. Additionally, hyperreactivity and difficulty with sleep induction were observed in 6-hydroxydopaminelesioned rats, an animal model of attention-deficit hyperactivity disorder. This study shows for the first time that actigraphy can be successfully used for behavioral analysis in rodents. These rat models could be useful for analyzing the mechanisms involved in sleep disturbances and hyperactivity disorder.

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Caffeine improves attention deficit in neonatal 6-OHDA lesioned rats, an animal model of attention deficit hyperactivity disorder (ADHD)

Cited by 32 publications

References 29 publications

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

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

Caffeine increases the motivation to obtain non-drug reinforcers in rats

Sleep Disturbance and Hyperactivity Detected by Actigraphy in Rats with Allergic Rhinitis or Attention-Deficit Hyperactivity Disorder

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