Synergistic interaction between mazindol, an anorectic drug, and swim-stress on analgesic responses in the formalin test in mice.
The present study examined the interaction between mazindol (MZ), an anorectic drug extensively used in Brazil and opioid/non-opioid endogenous analgesic systems activated by swim-stress. Further, the role of opioid, dopamine and N-methyl-D-aspartate (NMDA) receptors in mediating the analgesic effect was evaluated. The stress-induced analgesia of a 3-min swimming at 32 degrees C (opioid/non-opioid) and 20 degrees C (non-opioid) were assessed using the formalin test. Male Swiss mice were intraperitoneally injected with naloxone (1.0 mg/kg), sulpiride (3.0 mg/kg), MK-801 (0.075 mg/kg) or saline/vehicle 15 min prior, and with MZ (0.5 mg/kg) or saline/vehicle 5 min prior to swimming. The dose of MZ (0.5 mg/kg) did not cause analgesic effect, however, the association of MZ and swim-stress at both temperatures displayed synergistic interaction on analgesia that was blocked by sulpiride and MK-801 but not by naloxone. The present results suggest that MZ and swim-stress acted synergistically on analgesic responses, involving mainly the non-opioid component and possibly mediated by dopamine D2 receptors and NMDA receptors.
Vendruscolo
Leandro Franco
LF
Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, R. Ferreira Lima, 82, Florianópolis, SC 88015-420, Brazil.
Takahashi
Reinaldo Naoto
RN
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D008454:Mazindol / Q000494:pharmacology*; D051379:Mice; D009292:Narcotic Antagonists / Q000494:pharmacology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D018847:Opioid Peptides / Q000378:metabolism*; D010146:Pain / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism; D013312:Stress, Physiological / Q000378:metabolism* / Q000503:physiopathology
D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D011954:Receptors, Dopamine; D016194:Receptors, N-Methyl-D-Aspartate; D011957:Receptors, Opioid; D008454:Mazindol; D004298:Dopamine