title: Discriminative stimulus properties of mitragynine (kratom) in rats.
abstract: BACKGROUND
  Mitragynine (MG) is the primary active alkaloid extracted from the leaves of Mitragyna speciosa or kratom and exhibits pharmacological activities mediated by opioid receptors. The plant has been traditionally used for its opium and psychostimulant-like effects to increase work efficiency or as a substitute in the self-treatment of opiate addiction.
  
  
  OBJECTIVE
  The present study was performed to investigate the discriminative stimulus effects of MG in rats. The pharmacological mechanism of MG action and its derivative, 7-hydroxymitragynine (7-HMG) with a specific focus on opioid receptor involvement was examined in rats trained to discriminate morphine from vehicle. In order to study the dual actions of MG, the effect of cocaine substitution to the MG discriminative stimulus was also performed in MG-trained rats.
  
  
  METHODS
  Male Sprague Dawley rats were trained to discriminate MG from vehicle in a two-lever drug discrimination procedure under a tandem variable-interval (VI 60') fixed-ratio (FR 10) schedule of food reinforcement.
  
  
  RESULTS
  Rats acquired the MG discrimination (15.0 mg/kg, i.p.) which was similar to the acquisition of morphine discrimination (5.0 mg/kg, i.p.) in another group of rats. MG substituted fully to the morphine discriminative stimulus in a dose-dependent manner, suggesting pharmacological similarities between the two drugs. The administration of 7-HMG derivative in 3.0 mg/kg (i.p.) dose engendered full generalisation to the morphine discriminative stimulus. In addition, the MG stimulus also partially generalised to cocaine (10.0 mg/kg, i.p.) stimulus.
  
  
  CONCLUSIONS
  The present study demonstrates that the discriminative stimulus effect of MG possesses both opioid- and psychostimulant-like subjective effects.
authors.affiliation: Centre for Drug Research, Universiti Sains Malaysia, 11800, Gelugor, Penang, Malaysia. norsyifa.harun@gmail.com.
authors.forename: Norsyifa
authors.initials: N
authors.lastname: Harun
authors.affiliation: Centre for Drug Research, Universiti Sains Malaysia, 11800, Gelugor, Penang, Malaysia.
authors.forename: Zurina
authors.initials: Z
authors.lastname: Hassan
authors.affiliation: Centre for Drug Research, Universiti Sains Malaysia, 11800, Gelugor, Penang, Malaysia.
authors.forename: Visweswaran
authors.initials: V
authors.lastname: Navaratnam
authors.affiliation: Centre for Drug Research, Universiti Sains Malaysia, 11800, Gelugor, Penang, Malaysia.
authors.forename: Sharif M
authors.initials: SM
authors.lastname: Mansor
authors.affiliation: Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Shoaib
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D004193:Discrimination Learning / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009020:Morphine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000502:physiology; D046948:Secologanin Tryptamine Alkaloids / Q000494:pharmacology*
chemical_list: D000701:Analgesics, Opioid; D000697:Central Nervous System Stimulants; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D046948:Secologanin Tryptamine Alkaloids; C482678:7-hydroxymitragynine; D009020:Morphine; C001801:mitragynine; D003042:Cocaine
keywords: Cocaine; Drug discrimination; Kratom; Mitragynine; Morphine; Opioid; Rats