title: Differential effects of acute and chronic treatment with the α2-adrenergic agonist, lofexidine, on cocaine self-administration in rhesus monkeys.
abstract: BACKGROUND
  Lofexidine, an α2-adrenergic agonist, is being investigated as a treatment for reducing opioid withdrawal symptoms and blocking stress-induced relapse to cocaine taking. Opioid abusers are often polydrug abusers and cocaine is one frequent drug of choice. However, relatively little is known about lofexidine interactions with cocaine. The present study investigated the effects of acute and chronic treatment with lofexidine in a pre-clinical model of cocaine self-administration.
  
  
  METHODS
  Male rhesus monkeys were trained to respond for food (1g) and cocaine (0.01 mg/kg/injection) under a fixed ratio 30 (FR30) or a second order FR2 (VR16:S) schedule of reinforcement. Systematic observations of behavior were conducted during and after chronic treatment with lofexidine.
  
  
  RESULTS
  Acute treatment with lofexidine (0.1 or 0.32 mg/kg, IM) significantly reduced cocaine self-administration but responding for food was less effected. In contrast, chronic treatment (7-10 days) with lofexidine (0.1-0.32 mg/kg/h, IV) produced a leftward shift in the cocaine self-administration dose-effect curve, but had no effect on food-maintained responding. Lofexidine did not produce any observable side effects during or after treatment.
  
  
  CONCLUSIONS
  Lofexidine potentiated cocaine's reinforcing effects during chronic treatment. These data suggest that it is unlikely to be effective as a cocaine abuse medication and could enhance risk for cocaine abuse in polydrug abusers.
authors.affiliation: Alcohol and Drug Abuse Research Center, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA. Electronic address: skohut@mclean.harvard.edu.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kohut
authors.forename: Peter A
authors.initials: PA
authors.lastname: Fivel
authors.forename: Nancy K
authors.initials: NK
authors.lastname: Mello
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002406:Catheterization, Peripheral; D003000:Clonidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000523:psychology; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005502:Food; D008253:Macaca mulatta; D008297:Male; D012055:Reinforcement Schedule; D012646:Self Administration
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D003000:Clonidine; C025655:lofexidine
keywords: Adrenergic agonists; Behavioral observations; Cocaine; Lofexidine; Self-administration