Assessing acute effects of methylphenidate and modafinil on inhibitory capacity, time estimation, attentional lapses, and compulsive-like behavior in rats

• Published in: Behavioural pharmacology Vol. 36; no. 2-3; p. 76
• Main Authors: Sosa, Rodrigo, Espinosa-Villafranca, Pedro, Saavedra, Pablo, Chávez-Hernández, María Elena, Leal-Galicia, Perla, Lago, Gustavo, Mata, Florencia, Mata-Luévanos, Jesús, Rodríguez-Serrano, Luis Miguel, Tapia-De-Jesús, Alejandro, Buenrostro-Jáuregui, Mario
• Format: Journal Article
• Language: English
• Published: England 01.04.2025
• Subjects: Animals; Attention - drug effects; Behavior, Animal - drug effects; Benzhydryl Compounds - pharmacology; Central Nervous System Stimulants - pharmacology; Compulsive Behavior - drug therapy; Conditioning, Operant - drug effects; Impulsive Behavior - drug effects; Inhibition, Psychological; Male; Methylphenidate - pharmacology; Modafinil - pharmacology; Nootropic Agents - pharmacology; Rats; Rats, Inbred Lew; Rats, Wistar; Reward; Time Perception - drug effects; Wakefulness-Promoting Agents - pharmacology
• ISSN: 1473-5849
• DOI: 10.1097/FBP.0000000000000815

Medications known as 'cognitive enhancers' are increasingly being consumed off-label by healthy people, raising concerns about their safety. The aim of our study was to profile behavioral performance upon oral administration of methylphenidate (2.5 mg/kg) and modafinil (64 mg/kg) - two popular cognitive enhancers - and upon their discontinuation. We modeled cognitively demanding challenges in neurotypical individuals using a behavioral task where Wistar - Lewis rats had to withhold responses for a specified time to obtain food rewards. This task allowed us to extract several measures of behavioral performance associated with clinically meaningful indices, such as compulsive-like responding, incapacity to wait (impulsivity), time estimation (precision and accuracy), and attentional lapses. Our study design involved examining these behavioral indices in subjects administered either methylphenidate, modafinil, or vehicle. We found that subjects administered modafinil obtained fewer rewards and were less efficient in reward pursuing than the vehicle group; this result was likely due to a drug-induced inability to wait. Upon modafinil discontinuation, subjects earned more rewards but did not entirely catch up with the vehicle group. As for methylphenidate, neither favorable nor unfavorable effects were found in our main analyses. However, an exploratory analysis of changes in behavioral performance within sessions suggested that methylphenidate fostered favorable, yet short-lived, effects. We discuss our results in terms of the risks and cost-benefits of doses above or below the effective dose of cognitive enhancement drugs.