Sertraline dose-dependently increased the locomotor stimulating effect of amphetamine. At the highest dose, 20 mg/kg sertraline had a biphasic effect on amphetamine-induced hyperactivity, producing an initial reduction in amphetamine-induced hyperactivity that was later followed by an augmentation of amphetamine-induced hyperactivity in the last hour of the 3-h test. Sertraline, at doses of 5 and 10 mg/kg, produced an augmentation of amphetamine-induced hyperactivity over the last 2 h of the 3-h test session. Further, there was an increase in the concentration of amphetamine in the brain in rats pretreated with 5 mg/kg sertraline. Both sertraline (5 mg/kg) and fluoxetine (5 mg/kg) produced an augmentation of amphetamine-induced hyperactivity that was unaltered by a serotonergic lesion of the median and dorsal raphé nuclei that resulted in a greater than 90% depletion of serotonin in hippocampus, striatum, and nucleus accumbens. Further, both sertraline and fluoxetine inhibited spontaneous locomotor activity and this effect was also unaltered by the depletion of serotonin. Thus, serotonergic neurotransmission is not essential for the effects of sertraline and fluoxetine on spontaneous and amphetamine-induced locomotion. It is probable that sertraline and fluoxetine augment the locomotor stimulatory effect of amphetamine by decreasing the metabolism of amphetamine, perhaps via actions on cytochrome P450 isozymes.
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Similar content being viewed by others Explore related subjectsDiscover the latest articles and news from researchers in related subjects, suggested using machine learning. Author information Authors and AffiliationsBiopsychology Section, Centre for Mental Health and Drug Addiction, Clark Division, 250 College Street Toronto, Toronto, Canada M5T 1R e-mail: terrence@paych.toronto.edu, Fax:+1-416-979-6889, , , , , , CA
T. L. Sills & P. J. Fletcher
Neurochemical Research Unit, Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada T6G 2R7, , , , , , CA
A. J. Greenshaw & G. B. Baker
Received: 15 October 1998/Final version: 24 November 1998
About this article Cite this articleSills, T., Greenshaw, A., Baker, G. et al. The potentiating effect of sertraline and fluoxetine on amphetamine-induced locomotor activity is not mediated by serotonin. Psychopharmacology 143, 426–432 (1999). https://doi.org/10.1007/s002130050968
Issue Date: April 1999
DOI: https://doi.org/10.1007/s002130050968
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