Opioid and monoamine systems mediate the discriminative stimulus of tramadol in rats.
We analyzed the ability of the mu opioid peptide receptor ligands morphine and naloxone and several antidepressant drugs that are serotonin (fluoxetine), noradrenaline (reboxetine), mixed serotonin and noradrenaline (milnacipram and venlafaxine), dopamine (nomifensine) reuptake inhibitors, as well as roxindole (a nonselective drug) to substitute for, or alter, tramadol discrimination. Male Wistar rats were trained to discriminate tramadol (20 mg/kg) from saline in a two-choice water-reinforced paradigm. Out of the drugs studied, only morphine substituted for tramadol. In combination experiments, naloxone (0.1-1 mg/kg) attenuated the stimulus effects of tramadol (20 mg/kg) and the substitution evoked by morphine (2 mg/kg). Milnacipram (10 mg/kg) or reboxetine (10 mg/kg) enhanced the effects of tramadol (2.5-10 mg/kg); the other antidepressant drugs used failed to modulate tramadol discrimination. Our results indicate that tramadol can be used as a stimulus cue in rats, and that mu opioid peptide mechanisms are involved in its effects, while noradrenergic uptake inhibitors can enhance tramadol discrimination.
Filip
Małgorzata
M
Department of Pharmacology, Institute of Pharmacology Polish Academy of Sciences, 31-343 Kraków, 12 Smetna, Poland. filip@if-pan.krakow.pl
Wydra
Karolina
K
Inan
Salim Yalcin
SY
Dziedzicka-Wasylewska
Marta
M
Przegaliński
Edmund
E
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D015306:Biogenic Monoamines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003216:Conditioning, Operant; D003511:Cyclohexanols / Q000494:pharmacology; D003521:Cyclopropanes / Q000494:pharmacology; D004192:Discrimination, Psychological / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005473:Fluoxetine / Q000494:pharmacology; D008297:Male; D000078764:Milnacipran; D009020:Morphine / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009627:Nomifensine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000077593:Reboxetine; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology; D014147:Tramadol / Q000494:pharmacology*; D000069470:Venlafaxine Hydrochloride
D018759:Adrenergic Uptake Inhibitors; D000701:Analgesics, Opioid; D000928:Antidepressive Agents; D015306:Biogenic Monoamines; D003511:Cyclohexanols; D003521:Cyclopropanes; D018765:Dopamine Uptake Inhibitors; D005473:Fluoxetine; D000078764:Milnacipran; D009020:Morphine; D009025:Morpholines; D009270:Naloxone; D009292:Narcotic Antagonists; D009627:Nomifensine; D000077593:Reboxetine; D017450:Receptors, Opioid, mu; D017367:Selective Serotonin Reuptake Inhibitors; D012965:Sodium Chloride; D014147:Tramadol; D000069470:Venlafaxine Hydrochloride