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The Acute Effects of Amphetamine Derivatives on Extracellular Serotonin and Dopamine Levels in Rat Nucleus Accumbens

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Abstract

KANKAANPÄÄ, A., E. MERIRINNE, P. LILLSUNDE AND T. SEPPÄLÄ. The acute effects of amphetamine derivatives on extracellular serotonin and dopamine levels in rat nucleus accumbens. 〈Default ¶ Font>PHARMACOL BIOCHEM BEHAV 59(4) 1003–1009, 1998.—The acute effects of amphetamine derivatives on extracellular concentration of serotonin (5-HT) and dopamine in the nucleus accumbens were studied with in vivo microdialysis using conscious, freely moving rats. 5-HT, dopamine, and their major metabolites were measured by HPLC with electrochemical detection. Amphetamine (1.0–9.0 mg/kg) elevated dopamine levels considerably, but failed to affect the levels of 5-HT, except at the highest dose administered. 3,4-Methylenedioxyamphetamine (MDA, 1.0–9.0 mg/kg) and 3,4-methylenedioxymethamphetamine (MDMA, 1.0–9.0 mg/kg) elevated both 5-HT and dopamine levels dose dependently. The failure of 2,5-dimethoxy-4-methylamphetamine (DOM, 0.5–1.0 mg/kg) to affect the 5-HT levels suggests that extracellular levels of 5-HT play a minor role in hallucinogenic activity. The strong effects of MDA and MDMA on levels of 5-HT indicate that their actions on serotonergic mechanisms are different from those of the hallucinogens. In addition, methylenedioxyamphetamines may act via dopaminergic mechanisms similar to those of amphetamine.

Section snippets

Subjects

Adult male Wistar rats aged 11–12 weeks were used in the study. The rats were delivered from Helsinki University Laboratory Animal Centre, Finland, at least 1 week before the experiments. The total number of individuals was 125, and they were housed two per cage in a temperature-controlled room with a light cycle of 12 h, and free access to food and water. The experimental setup was approved by the Committee for Animal Experiments of the National Public Health Institute.

Drugs

Amphetamine sulphate

Results

The means of basal concentrations in dialysate were as follows (±SE; n = 25): dopamine 157 ± 21 fmol/60 μl, 5-HT 73 ± 11 fmol/60 μl, DOPAC 24.8 ± 2.8 pmol/60 μl, HVA 10.0 ± 1.2 pmol/60 μl, and 5-HIAA 6.5 ± 0.4 pmol/60 μl. The baseline levels remained unaltered in saline-treated rats.

Discussion

As measured by this in vivo microdialysis study, the amphetamine derivatives elevated the extracellular 5-HT levels in nucleus accumbens in the following order of magnitude: MDMA > MDA > amphetamine > DOM. For elevation of the dopamine levels the corresponding order is: amphetamine > MDMA = MDA > DOM. Thus, amphetamine predominantly elevated the dopamine levels, while MDA and MDMA elevated both the 5-HT and dopamine levels, and DOM failed to affect either of the compounds markedly. These

Acknowledgements

The authors wish to thank Ms. Riitta Tirkkonen-Vesikko for her capable technical assistance.

References (31)

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