title: Oral modafinil facilitates intracranial self-stimulation in rats: comparison with methylphenidate.
abstract: Modafinil is a low-potency inhibitor of dopamine transporters (DAT) approved clinically to promote wakefulness. In most procedures used for abuse-liability assessment, modafinil produces effects similar to those of abused DAT inhibitors such as cocaine and methylphenidate, although modafinil often shows lower effectiveness. However, modafinil has failed to maintain drug self-administration or produce conditioned place preferences in rats. The low potency and poor solubility of modafinil complicate its delivery by parenteral routes of administration commonly used in rats, and this may contribute toward negative results. This study evaluated the effects of orally administered modafinil in rats using an assay of intracranial self-stimulation (ICSS) that has been used to examine the effects of other DAT inhibitors. Adult male Sprague-Dawley rats equipped with electrodes in the medial forebrain bundle responded for pulses of brain stimulation that varied across a range of frequencies (158-56 Hz) during daily behavioral sessions. Modafinil (20-600 mg/kg, orally) and methylphenidate (1.0-10 mg/kg, intraperitoneally; 3.2-32 mg/kg, orally) produced dose-dependent and time-dependent facilitation of ICSS, an effect produced by abused DAT inhibitors and other classes of abused drugs. These results are in agreement with other evidence for stimulant-like abuse liability of modafinil and show the sensitivity of ICSS to orally administered drug.
authors.affiliation: Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Lazenka
authors.forename: S Stevens
authors.initials: SS
authors.lastname: Negus
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects; D008774:Methylphenidate / Q000008:administration & dosage / Q000494:pharmacology*; D000077408:Modafinil; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D012653:Self Stimulation / Q000187:drug effects*; D013997:Time Factors; D064690:Wakefulness-Promoting Agents / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D064690:Wakefulness-Promoting Agents; D008774:Methylphenidate; D000077408:Modafinil