Elsevier

Brain Research

Volume 591, Issue 2, 25 September 1992, Pages 319-326
Brain Research

Research report
Role of catecholamines in the modafinil and amphetamine induced wakefulness, a comparative pharmacological study in the cat

https://doi.org/10.1016/0006-8993(92)91713-OGet rights and content

Abstract

Seventeen adult cats were chronically implanted with electrodes for polygraphic recordings in order to assess the role of catecholamines in the arousal effects of oral administrations of modafinil, a presumed noradrenergic agonist, and amphetamine, a well-known catecholamine-releasing agent. Whereas both modafinil (1, 2.5 and 5 mg/kg) and amphetamine (0.25, 0.5 and 1 mg/kg) caused a significant and dose-dependent increase in wakefulness and brain temperature, amphetamine, but not modafinil, elicited marked signs of behavioral excitation. Pretreatments with α-methyl-dl-p-tyrosine methyl ester (50 mg/kg, i.p.), an inhibitor of catecholamine synthesis, almost completely prevented the effects of amphetamine (0.25 and 1 mg/kg), but only slightly reduced the duration of the waking effect of modafinil (2.5 and 5 mg/kg). Pretreatments with phentolamine (10 mg/kg, i.p.), prazosin (1.5 mg/kg, per os) and propranolol (5 mg/kg, i.p.), an α-, α1 and β-receptor antagonists, respectively, attenuated significantly the arousal effect of modafinil (1 mg/kg, the same as below) but not of amphetamine (0.25 mg/kg, the same as below). Intraperitoneal injections of haloperidol (0.5 mg/kg), a dopamine-receptor antagonists, blocked significantly the arousal of amphetamine but not of modafinil. The effects of both modafinil and amphetamine were enhanced by a pretreatment with yohimbine (1 mg/kg, i.p.), an α2-receptor antagonist. These results suggest that the arousal effect of modafinil does not depend on the availability of the endogenous catecholamines but results from an enhancement of α1 and β-receptor activity and that the waking and behavioral effects of amphetamine may be mainly due to an increase in dopamine release.

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