Ishizuka and colleagues found that both 75 and 150 mg/kg of modafinil significantly increased locomotor activity and histamine release. The behavioral effects of 150 mg/kg of modafinil were found to be similar to 3 mg/kg of methylphenidate. To further parse out the effects of histamine on locomotor activity, the researchers administered α-fluoromethylhistidine (an irreversible inhibitor of histamine synthesis) to deplete neuronal histamine in the rats. They found that this completely extinguished the locomotor activity-enhancing effects of modafinil, while having no effect on methylphenidate stimulation. In conclusion, they suggest the enhancement of locomotor activity by modafinil, but not methylphenidate, is intimately involved with central histaminergic systems.
In a 2014 rat study, Ornell et al. examined the behavioral effects of modafinil in an open field test. The researchers administered 75, 150, and 300 mg/kg of modafinil and evaluated locomotor activity in the Open Field at varying time points.
The researchers found that only the 300 mg/kg dose of modafinil increased locomotor activity 1 and 3 hours after administration, with increased visits to the center of the open field 1 hour after administration. However, 3 hours after modafinil administration, all of the modafinil doses increased visits to the center of the Open Field. In summary, the researchers note that high dose modafinil (300mg /kg) induces hyperactivity in the Open Field. In addition, modafinil produces anxiolytic effects across all doses, as seen by increased visits to the center of the Open Field.
Effects on Memory
In this section, we will overview buying modafinil online effects on working memory in healthy, chronically-stressed, and sleep-deprived mice. Both stress and sleep deprivation are well known to negatively impact working memory performance in humans and other animals. These mice models offer insight into how modafinil interacts with conditions that humans are commonly subjected to when taking modafinil.
Effects on Working Memory in Healthy Mice
Beracochea et al. examined the effects of modafinil on working memory in C57BL/6 mice in a sequential alternation task. The researchers administered a pretest injection of varying doses of modafinil (8 mg/kg, 32mg/kg, and 64 mg/kg) and assessed its effects on delayed spontaneous alternation rates.
They found that 64 mg/kg, but not 8 mg/kg or 32 mg/kg, significantly increased alternation scores when compared to controls. Specifically, the researchers found that 64 mg/kg produced a delay-dependent enhancement in working memory performance by increasing alternation rates mainly at long (60s and 180s) intertrial intervals. In conclusion, the researchers state that modafinil produces a dose- and delay-dependent enhancement of working memory. These effects did not extend to exploratory or anxiety-related activity as measured in a four hole-board apparatus.
Effects on Working Memory in Chronically-Stressed Mice
Modafinil may enhance psychomotor performance and memory in part by increasing glucocorticoid secretion through the adrenal cortex. Glucocorticoids (such as cortisol in humans and corticosterone in rodents) play an important role in mediating learning and memory processes.
Pierard and colleagues examined the dose-effect relationship of modafinil on working memory and psychomotor performance, alongside measurements of plasma corticosterone in chronically-stressed mice. Researchers administered a control or modafinil (8, 16, or 32 mg/kg) after or without chronic stress. The rats were stressed via immobilization in a Plexiglass tube under high light exposure for 15 min/day over 14 consecutive days. Memory performance was evaluated by spontaneous alternation in a T-maze.
The researchers observed that optimal working memory performance was produced from the 16 mg/kg dose under non-stress conditions. Both the 16 mg/kg and 32 mg/kg doses of modafinil significantly increased corticosterone levels. However, working memory performance and plasma corticosterone levels appeared to be uncorrelated.
Under stress conditions, the researchers found that, compared to non-stressed animals, 8mg/kg of modafinil increased working memory performance while the higher doses of 16 mg/kg and 32 mg/kg decreased memory performance. These results indicate that stress lowers the efficiency threshold of modafinil, thereby inducing the most optimal psychomotor performance at low dosages. Concurrent measurements of plasma corticosterone levels revealed that 8 mg/kg lowered corticosterone levels while the higher doses did not affect levels.
Thus, working memory performance appeared to be inversely correlated with plasma corticosterone levels in the stressed condition. In light of this data, the researchers hypothesize that high doses of modafinil could impair performance in humans subjected to stressful conditions (such as seen in sports performance).
Effects on Working Memory in Sleep-Deprived Mice
Given that buy modafinil online is effective in promoting alertness and performance in sleep-disordered patients, modafinil’s efficacy in reversing cognitive impairment due to sleep deprivation has been investigated by a number of researchers.
In one 2007 study, Pierard and colleagues investigated the effects of modafinil on spatial working memory in sleep-deprived mice. The researchers assessed delay-dependent working memory with spontaneous alternation behavior in a T-maze.
To induce sleep deprivation, the researchers used an original total sleep deprivation apparatus validated with EEG recordings. This automated, low-stress apparatus consists of a water box with two platforms that continuously move above and below the surface of the water, forcing the mouse to move back and forth every 10 seconds to avoid water contact.
Firstly, the researchers found that diurnal 10-hour sleep deprivation produces impairments in spatial working memory, seen as reduced alternation rates compared to the non-sleep-deprived control group.]to examine the effects of sleep deprivation on neural activity, they quantified the c-Fos protein in various cerebral zones. Sleep deprivation decreased c-Fos expression in the anterior hypothalamus and supraoptic nucleus, two regions involved in wake-sleep cycle regulation. They also found reduced c-Fos staining in the frontal cortex and hippocampus (involved in memory) and the amygdala (involved in emotions).
The researchers then assessed the effects of modafinil after the 10-hour sleep deprivation period. They found that 64 mg/kg, but not 32 mg/kg, significantly increased alternation rates that were previously impaired by sleep deprivation. Increased spontaneous alternation indicates the rodent better remembered which arm it had last visited. Interestingly, the 64 mg/kg dose of modafinil restored neural activity in the same brain regions previously disrupted by sleep deprivation. The researchers note that the anxiety-like action of modafinil may contribute to the effects on neural activity they observed. In conclusion, modafinil was able to rescue the memory-impairing effects of 10 hours of sleep deprivation and restore normal levels of neural activity in various brain regions affected by sleep deprivation
