| Summary: | Treatments for cognitive impairments associated with neuropsychiatric disorders, such as attention deficit hyperactivity disorder or narcolepsy, aim at modulating extracellular dopamine levels in the brain. CE-123 (5-((benzhydrylsulfinyl)methyl) thiazole) is a novel modafinil analog with improved specificity and efficacy for dopamine transporter inhibition that improves cognitive and motivational processes in experimental animals. We studied the neuropharmacological and behavioral effects of the <i>S</i>-enantiomer of CE-123 ((<i>S</i>)-CE-123) and <i>R</i>-modafinil in cognitive- and reward-related brain areas of adult male rats. In vivo single unit recordings in anesthetized animals showed that (<i>S</i>)-CE-123, but not <i>R</i>-modafinil, dose-dependently (1.25 to 10 mg/kg i.v.) reduced firing of pyramidal neurons in the infralimbic/prelimbic (IL/PrL) cortex. Neither compound the affected firing activity of ventral tegmental area dopamine cells. In freely moving animals, (<i>S</i>)-CE-123 (10 mg/kg i.p.) increased extracellular dopamine levels in the IL/PrL, with different patterns when compared to <i>R</i>-modafinil (10 mg/kg i.p.); in the nucleus accumbens shell, a low and transitory increase of dopamine was observed only after (<i>S</i>)-CE-123. Neither (<i>S</i>)-CE-123 nor <i>R</i>-modafinil initiated the emission of 50-kHz ultrasonic vocalizations, a behavioral marker of positive affect and drug-mediated reward. Our data support previous reports of the procognitive effects of (<i>S</i>)-CE-123, and show a minor impact on reward-related dopaminergic areas.
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