The stimulatory effects of caffeine with oseltamivir (Tamiflu®) on light–dark behavior and open-field behavior in mice

Caffeine stimulates locomotor activity in the mammalian spinal cord via adenosine A1 receptor-dopamine D1 receptor interaction and PKA-dependent mechanisms

“…The cessation of locomotor activity at higher concentrations of caffeine raises the possibility that caffeine can have an “inverted U shape” dose dependent-effect in the spinal locomotor function similar to reported effects of systemic application of this drug producing an increase in locomotor activity in freely behaving animals (Kuribara et al, 1992; Nehlig et al, 1992; Haghgoo et al, 1995; Soares et al, 2009). These studies suggested that caffeine exerts a stimulating effect on locomotor activity at low to moderate doses, but less stimulating and even depressive effects at higher doses (Mumford and Holtzman, 1991; El Yacoubi et al, 2000; Malec and Poleszak, 2006; Uchiyama et al, 2010; Zhang et al 2011). …”

“…Increased locomotor activity of a freely behaving rodent in the central region of an open field or a greater ratio to total locomotion is used as an indicator for evaluating anxiogenic or anxiolytic properties (Prut and Belzung, 2003). Caffeine has been shown to promote anxiogenic-like behavior in the light–dark preference test (Uchiyama et al, 2010). Additionally, caffeine was shown to increase locomotor activity in the open field (Kuribara et al, 1992; Nehlig et al, 1992; Haghgoo et al, 1995; Soares et al, 2009) in a bell-shaped dose-dependent manner.…”

“…The results prompted us to explore if caffeine can modulate locomotor behavior when applied directly to the isolated spinal cord of mice, and if so, is this effect through the antagonism of adenosine receptors as previously reported in the brain? (El Yacoubi et al, 2000; Malec and Poleszak, 2006; Mumford and Holtzman, 1991; Uchiyama et al, 2010; Zhang et al 2011). We report that addition of caffeine to the superfusate of an isolated lumbar spinal cord preparation, in the presence of a locomotor-like pattern induced by a combination of serotonin (5-TH), the glutamate analog n-methyl-d-aspartate (NMDA) and dopamine, had a stimulating effect by significantly decreasing the cycle period of the locomotor pattern, while decreasing motorneuron burst duration in most preparations in a reversible manner.…”

Effect of adenosine system in the action of oseltamivir on behavior in mice

“…Furthermore, motor activation following systemic administration of caffeine has been associated with dopamine release in the nucleus accumbens [27]. We reported previously the actions of oseltamivir involve an effect on locomotion, with low doses associated with an increase in locomotor activity by caffeine [28]. These data suggest that the actions of oseltamivir may involve the dopaminergic system, while being modulated by caffeine due to its stimulating effect on dopamine release.…”

“…Caffeine is a non-selective adenosine A 1 /A 2 receptor antagonist with similar affinity for both receptors [7]. Previously, we reported that the action of oseltamivir involves the adenosine systems [28]. However, the effects of caffeine remain to be clarified with respect to the aberrant behaviors induced by oseltamivir.…”