title: Effects of the dopamine/norepinephrine releaser phenmetrazine on cocaine self-administration and cocaine-primed reinstatement in rats.
abstract: BACKGROUND
  Like other monoamine releasers such as D-amphetamine, chronic treatment with phenmetrazine can attenuate cocaine self-administration in monkeys.
  
  
  OBJECTIVE
  The present studies extended this finding to rodents and to cocaine-primed reinstatement, a putative laboratory animal model of relapse.
  
  
  METHODS
  In experiment 1, rats self-administered food pellets or injections of 0.19 mg/kg cocaine (i.v.) under a progressive-ratio schedule. When responding was stable, subcutaneous osmotic pumps were implanted containing saline or (+)-phenmetrazine (25 or 50 mg/kg per day). In experiment 2, rats self-administered injections of 0.75 mg/kg cocaine under a fixed-ratio 1 schedule in daily 6-h sessions. When responding was stable, rats were removed from the self-administration environment for 7 days and treated continuously with saline, 5 mg/kg per day D-amphetamine or phenmetrazine (25 or 50 mg/kg per day) via osmotic pumps. Rats were then returned to the self-administration context while treatment continued, and responding was extinguished by removing response-contingent stimulus changes and cocaine injections. Once responding was extinguished, reinstatement tests were conducted using cocaine injections (10 mg/kg i.p.).
  
  
  RESULTS
  Phenmetrazine decreased self-administration of cocaine, but not food pellets, during the 14-day treatment period; effects persisted for several days after treatment was discontinued. Moreover, cocaine-induced increases in responding during the reinstatement test were attenuated by D-amphetamine and both phenmetrazine doses.
  
  
  CONCLUSIONS
  These results extend the study of the effects of phenmetrazine on cocaine self-administration to a rodent model, and provide further support for the use of monoamine releasers as agonist medications for cocaine abuse.
authors: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA. pczoty@wakehealth.edu.
authors: Paul W
authors: PW
authors: Czoty
authors: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
authors: Phuong
authors: P
authors: Tran
authors: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
authors: Leanne N
authors: LN
authors: Thomas
authors: Pain Mechanisms Laboratory, Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
authors: Thomas J
authors: TJ
authors: Martin
authors: Pain Mechanisms Laboratory, Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
authors: Amanda
authors: A
authors: Grigg
authors: Center for Organic and Medicinal Chemistry, Research Triangle Institute, P.O. Box 12194, Research Triangle Park, NC, 27709, USA.
authors: Bruce E
authors: BE
authors: Blough
authors: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.|Ferring Pharmaceuticals, Clinical Sciences, 100 Interpace Parkway, Parsippany, NJ, 07054, USA.
authors: Thomas J R
authors: TJ
authors: Beveridge
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000188:drug therapy / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004435:Eating / Q000187:drug effects / Q000502:physiology; D008253:Macaca mulatta; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010633:Phenmetrazine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012646:Self Administration
chemical_list: D003042:Cocaine; D004298:Dopamine; D009638:Norepinephrine; D010633:Phenmetrazine
keywords: Agonist therapy; Monoamine; Rat; Reinforcement; Reinstatement; Relapse