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Effects of amphetamine, methylphenidate, and apomorphine on regional brain serotonin and 5-hydroxyindole acetic acid

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Abstract

Electrophysiological and cytofluorometric data suggest that doses of amphetamine which enhance locomotor activity and promote focused stereotypies produce pronounced effects on serotonin pathways in the CNS. However, the biochemical evidence regarding changes in serotonergic function produced by moderate doses of this drug is inconsistent. Therefore, the present study was designed to further examine the effects of amphetamine (1–5 mg/kg) on regional brain serotonin and its metabolite and to compare these effects to behaviorally comparable doses of methylphenidate and apomorphine. At doses which produce a multiphasic behavioral response pattern, including a stereotypy phase consisting primarily of repetitive head movements and occasional oral stereotypies, amphetamine (3 mg/kg) and methylphenidate (30 mg/kg) increased levels of 5HIAA in striatum and frontal cortex, two brain regions which receive serotonergic projections from the dorsal raphe nucleus. In contrast, these drugs decreased or had no effect on 5HIAA levels in hippocampus, a brain region which receives its serotonergic innervation from the median raphe nucleus. A moderate dose of apomorphine (0.5 mg/kg) produced a comparable pattern of neurochemical effects. These data are consistent with electrophysiological and cytofluorometric data suggesting enhanced dorsal raphe serotonergic function following amphetamine-like stimulants. Pretreatment of animals with α-methyltyrosine at a dose sufficient to prevent the locomotor stimulation and stereotypy promoted by amphetamine, or by haloperidol, failed to prevent the amphetamine-induced increase in 5HIAA, indicating that these serotonergic effects are not secondary to the amphetamine facilitation of dopaminergic transmission. The results of this study suggest that serotonin may play a modulatory role in the behavioral effects of amphetamine-like stimulants which is dependent for its expression on an intact dopamine system.

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Abbreviations

DA:

dopamine

AMPH:

S(+)amphetamine

5HT:

serotonin

MP:

methylphenidate

APO:

apomorphine

5HIAA:

5-hydroxyindoleacetic acid

αMT:

α-methyltyrosine

DOPAC:

3,4-dihydroxyphenylacetic acid

HVA:

homovanillic acid

HAL:

haloperidol

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Author notes

  1. N. J. Leith

    Present address: Searle Research and Development, Division of G.D. Searle and Co., CNS Pharmacology, 4901 Searle Parkway, 60077, Skokie, IL, USA

  2. C. D. Applegate

    Present address: Department of Neurology, G-310, Childrens' Hospital, 300 Longwood Avenue, 02115, Boston, MA, USA

Authors and Affiliations

  1. Department of Psychiatry, University of California, San Diego, 92093, La Jolla, CA, USA

    R. Kuczenski & D. S. Segal

  2. Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA

    R. Kuczenski, N. J. Leith & C. D. Applegate

Authors
  1. R. Kuczenski
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  2. D. S. Segal
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  3. N. J. Leith
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  4. C. D. Applegate
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Kuczenski, R., Segal, D.S., Leith, N.J. et al. Effects of amphetamine, methylphenidate, and apomorphine on regional brain serotonin and 5-hydroxyindole acetic acid. Psychopharmacology 93, 329–335 (1987). https://doi.org/10.1007/BF00187252

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  • DOI: https://doi.org/10.1007/BF00187252

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