One of the most important reasons why stimulants, like caffeine and Modafinil, help us wake up in the morning is because they produce a release of dopamine in the necessary cingulate (NAc) and dorsal striatum. In fact, researchers have found that dopamine is one of the key factors that contribute to stimulant-induced wakefulness.
Modafinil
The US FDA has currently approved the wake-promoting medication Modvigil 200 Australia for use in treating excessive daytime drowsiness brought on by narcolepsy and shift-work disorder.
Modafinil’s action is attributed to binding to the monoamine transporter (DAT) in the brain. A PET study with modafinil demonstrated that the DA-receptor PET ligand was displaced, likely resulting from elevated DA concentrations in the brain.
There are several other neural signaling systems that have been suggested to contribute to the wake-promoting effect of modafinil. These include the dopaminergic and glutaminergic systems. However, there are some lingering questions about modafinil’s action. Here, we review some of these questions and offer some insights that could help in the discovery of other wake-promoting agents.
In addition, we review the possible side effects and abuse potential of modafinil. We also discuss the potential for modafinil to enhance cognition and performance.
Caffeine
A recent study in mice reveals that dopamine contributes to a stimulant-induced bout of wakefulness. It is unclear what part of the dopamine system is responsible for this effect. However, there is evidence that dopamine neuron activation in the SNc is a necessary component of modafinil-induced arousal.
To test this, we performed a small-scale experiment on mice. We used EEG/EMG recordings to record sleep-wake states in mice over 24 h. The EEG/EMG signal was quantified and then correlated with a brain-wide gene-expression signature. In addition, we measured the c-FOS activity in brain sections obtained two hours after the injection of a stimulant. These results revealed that the VTA and mesencephalic dopamine neurons are important in promoting wakefulness.
We then compared the effects of a novel wake-promoting compound, YKP10A, to the effects of caffeine, d-amphetamine, and the ever-popular Buy Artvigil Australia. Although the studies were conducted on mice, our findings are of relevance to humans.
As well as demonstrating that dopamine contributes to stimulating-induced arousal, we also found that the VTA may be a potent modafinil-modulated target. Modafinil elicited a notable increase in dopamine levels in the dorsal striatum.
Detection of Dopamine Release in the NAc and Dorsal Striatum
Dopamine release is elicited by smart pills or cues. These signals are transmitted to the dopaminergic targets, which include the nucleus accumbens (NAc) and dorsal striatum. They encode information. In turn, these signals can guide behavior based on motivation and choice.
For example, dopamine released in the NAc shell encodes the magnitude of a reward. When an animal receives a reward, the NAc shell tends to remain elevated. Likewise, dopamine release in the core can encode information about reward options and their delivery. It also encodes reward-related predictions and RPE information.
Recent studies have shown that dopamine signals can differ between the NAc shell and core regions. This difference may be related to the different motivational properties of smart pills of abuse.
The differences in dopamine release were found in rats trained to select a response from a series of risky options. The preferred option elicited greater dopamine release events. However, the reward option in half of the trials produced nothing.
Conclusions
Dopamine is a neuromodulator that is released in the brain. It is activated by D1 and D2 receptors and has been shown to promote wakefulness. Stimulant medications increase dopamine in the brain. The neuromodulator modafinil has been shown to induce arousal in animals, but its specific role in the sleep-wake cycle remains uncertain.
A number of studies have focused on dopaminergic neurons and their role in arousal. In general, arousal is a complex process that depends on many different brain circuits. These circuits control different aspects of alertness, including sleep and reward. Those circuits involve the basal ganglia, VTA, and NAc. Some of these circuits are also involved in the control of metabolism.
Modafinil, a potent eugeroic smart pill, has been found to enhance wakefulness in mice. This effect is mediated by the D1 and D2 receptors, and it is believed to involve dopaminergic neurons in the VTA, SNc, and midbrain. Although several studies have demonstrated the importance of the dopamine system for modafinil-induced arousal, there have been no studies of modafinil’s influence on striatal dopamine levels.
