Long-term exposure of rats to tramadol alters brain dopamine and alpha 1-adrenoceptor function that may be related to antidepressant potency.
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.
Faron-Górecka
Agata
A
Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Kraków, Poland.
Kuśmider
Maciej
M
Inan
Salim Yalcin
SY
Siwanowicz
Joanna
J
Piwowarczyk
Teresa
T
Dziedzicka-Wasylewska
Marta
M
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D013995:Time; D014147:Tramadol / Q000008:administration & dosage* / Q000378:metabolism
D000928:Antidepressive Agents; D018340:Receptors, Adrenergic, alpha-1; D014147:Tramadol; D004298:Dopamine