title: Lack of sensitization during place conditioning in rats is consistent with the low abuse potential of tramadol.
abstract: Based on the recent finding that tramadol (TRAM) produces conditioned place preference (CPP) and dopamine release in the nucleus accumbens, it was suggested that the abuse liability of TRAM may be greater than hitherto assumed. We re-evaluated the effects of TRAM in CPP and behavioral sensitization, in comparison with morphine (MOR) and meptazinol (MEPT), an opioid drug with minimal abuse potential. While MOR produced CPP and very strong locomotor sensitization, TRAM and MEPT produced only CPP. It has been suggested that sensitization plays an important role in the development of addiction, hence our results suggest that the abuse potential of TRAM might resemble more that of MEPT than that of MOR, and they are consistent with the clinical picture, in that although TRAM is not completely devoid of positively reinforcing effects, reports on abuse are rare. The low propensity to induce addiction may be related to the lack of changes in the brain circuitry mediating reward and motivation, as evidenced by the lack of sensitization.
authors.affiliation: Grünenthal GmbH, Research and Development, Department of Pharmacology, Postfach 500444, 52088 Aachen, Germany. thomas.tzschentke@grunenthal.de
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Tzschentke
authors.forename: Walter
authors.initials: W
authors.lastname: Bruckmann
authors.forename: Elmar
authors.initials: E
authors.lastname: Friderichs
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003213:Conditioning, Psychological / Q000187:drug effects*; D008297:Male; D008621:Meptazinol / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009294:Narcotics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019966:Substance-Related Disorders / Q000503:physiopathology*; D014147:Tramadol / Q000494:pharmacology*
chemical_list: D009294:Narcotics; D008621:Meptazinol; D014147:Tramadol; D009020:Morphine