Related Experiment Videos
Awakening properties of modafinil: effect on nocturnal activity in monkeys (Macaca mulatta) after acute and repeated
J F Hermant1, F A Rambert, J Duteil
1Centre de Recherches du Laboratoire L. Lafon, Maisons-Alfort, France.
Abstract:
Single oral administration of modafinil (16-64 mg/kg) in monkeys induced an increase in nocturnal activity and in behavioural arousal without stereotyped behaviour. Modafinil-induced increase in nocturnal activity was prevented by the centrally acting alpha 1 adrenoceptor antagonist prazosin. After repeated oral administration of modafinil, b.i.d. for 5 days, nocturnal activity was still increased, but was lower than after a single administration; the gradual decrease appeared on the second night. No rebound of sleep and no residual effect on night 5 (when modafinil was administered for 4 days and placebo on day 5) were seen after the withdrawal of the drug. Therefore, modafinil appeared to produce strong behavioural stimulation and awakening in a non-human primate species, after single, as well as after repeated administration, without other obvious side-effects (no sign of anxiety, no behavioural trouble). These awakening properties involved a modulation (stimulation) of a central alpha 1 adrenergic system.
Insights
Modafinil increased nocturnal activity and behavioral arousal in monkeys without side effects. This effect involved the alpha-1 adrenergic system and persisted after repeated administration.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Modafinil is a wakefulness-promoting agent.
- Its mechanism of action, particularly in non-human primates, requires further elucidation.
- Understanding modafinil's effects on behavior and its underlying neurochemical pathways is crucial for its therapeutic applications.
Purpose of the Study:
- To investigate the behavioral effects of modafinil in a non-human primate model.
- To determine if modafinil induces arousal and activity without adverse behavioral changes.
- To explore the role of the alpha-1 adrenergic system in modafinil's effects.
Main Methods:
- Single and repeated oral administration of modafinil (16-64 mg/kg) to monkeys.
- Assessment of nocturnal activity and behavioral arousal.
- Administration of prazosin, an alpha-1 adrenoceptor antagonist, to evaluate its modulatory effect.
- Observation for side effects such as stereotyped behavior or anxiety.
Main Results:
- Modafinil significantly increased nocturnal activity and behavioral arousal.
- The effects were dose-dependent and persisted after repeated administration.
- Prazosin blocked the modafinil-induced increase in nocturnal activity.
- No stereotyped behavior or signs of anxiety were observed.
Conclusions:
- Modafinil promotes behavioral stimulation and wakefulness in non-human primates.
- These effects are mediated, at least in part, by the central alpha-1 adrenergic system.
- Modafinil appears to be well-tolerated, with a low incidence of adverse behavioral effects.