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Eur J Pharmacol. 2004 Oct 6;501(1-3):103-10.

Long-term exposure of rats to tramadol alters brain dopamine and alpha 1-adrenoceptor function that may be related to antidepressant potency.

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Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Kraków, Poland.


The aim of the present study was to determine whether tramadol, which has a potential antidepressant efficacy, evokes, when administered repeatedly, changes similar to the alterations induced by conventional antidepressant drugs. Repeated administration of tramadol (20 mg/kg i.p. for 21 days) enhanced the d-amphetamine-induced locomotor hyperactivity and increased the density of alpha(1)-adrenoceptors in the rat brain cortex, as measured by saturation analysis of [(3)H]prazosin binding. Autoradiographic analysis of [(3)H]7-OH-DPAT and [(3)H]raclopride binding revealed a significant up-regulation of dopamine D2 and D3 receptors in the rat nucleus accumbens upon repeated treatment with tramadol. All the above-mentioned effects induced by repeated administration of tramadol resemble the effects induced by conventional antidepressants. However, tramadol when administered repeatedly did not increase the levels of mRNA encoding for brain-derived neurotrophic factor (BDNF) and its receptor, TrkB. This is what differs tramadol from conventional antidepressants, since neurotrophic effects of these drugs have recently been postulated.

[Indexed for MEDLINE]

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