Objectives: These experiments investigated the effects of selective serotonin (5-HT) depletion on intravenous self-administration of d-amphetamine. Methods: Depletion of brain 5-HT levels was induced by injecting the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) into the dorsal and median raphe nuclei. Rats were then trained to self-administer d-amphetamine according to various schedule and access conditions via chronically indwelling intravenous catheters. Results: Large reductions of brain 5-HT did not alter responding for a training dose of 120 µg/kg d-amphetamine delivered according to a fixed ratio 1 schedule during 3-h sessions. When the dose of d-amphetamine was altered (0, 3.75, 7.5, 15, 30, 60 µg/kg per infusion) a characteristic inverted U-shaped dose response function was obtained. The 5-HT depleted rats showed increased responding for the lower doses of d-amphetamine, with a large significant increase in responding for the 7.5 µg/kg dose. In these same rats, the suppressive effect of 10 mg/kg fluoxetine on d-amphetamine (60 µg/kg) self-administration was prevented. The 5,7-DHT lesion also did not alter responding for d-amphetamine (120 µg/kg) in longer (8 h) daily access sessions. Responding for d-amphetamine delivered on a progressive ratio schedule, in which response requirements increased for each successive infusion of d-amphetamine, was also determined in 5-HT depleted rats. The number of d-amphetamine infusions was not different from the number of infusions earned by sham-lesioned rats across a range of doses of d-amphetamine (7.5–60 µg/kg). In a final experiment, spontaneous acquisition of self-administration of low doses of d-amphetamine (10 and 30 µg/kg) was measured in 5-HT depleted and control rats. Again, self-administration behaviour in the 5-HT depleted rats did not differ from controls. Conclusions: These results provide no evidence that reducing 5-HT function alters the primary reinforcing effects of self-administered amphetamine. The increase in self-administration of a low dose of amphetamine observed in experiment 1 probably involves some other process such as increased resistance to extinction.
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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 AffiliationsDepartments of Psychiatry and Psychology, University of Toronto, Centre for Addiction and Mental Health, Clarke Division, 250 College Street, Toronto, Ontario, Canada M5T 1R8 e-mail: fletcher@psych.toronto.edu Fax: +1-416-979-6942, , , , , , CA
P. J. Fletcher
Department of Psychology, University of Toronto, Centre for Addiction and Mental Health, Clarke Division, 250 College Street, Toronto, Ontario, Canada M5T 1R8, , , , , , CA
Karin M. Korth
Section of Biopsychology, Centre for Addiction and Mental Health, Clarke Division, 250 College Street, Toronto, Ontario, Canada M5T 1R8, , , , , , CA
John W. Chambers
Received: 28 December 1998 / Final version: 28 April 1999
About this article Cite this articleFletcher, P., Korth, K. & Chambers, J. Depletion of brain serotonin following intra-raphe injections. Psychopharmacology 146, 185–193 (1999). https://doi.org/10.1007/s002130051105
Issue Date: September 1999
DOI: https://doi.org/10.1007/s002130051105
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