title: Interest for delivery of cocaethylene in a sustained release emulsion vs saline evaluated on behavioral sensitization in naive and cocaine-sensitized mice.
abstract: BACKGROUND
  Repeated administration of psychostimulant elicits behavioral sensitization, characterized by an augmented locomotor response to a subsequent challenge injection. This sensitization is paralleled by neural adaptations. Evidences suggest that the rate at which drugs of abuse are delivered to the brain play a key role in this plasticity. Cocaethylene is a pharmacologically active homolog of cocaine, known to have a pharmacokinetic profile different to that of cocaine.
  
  
  OBJECTIVE
  Utilizing locomotor sensitization, we evaluated the consequences of the administration of cocaethylene in a rapid- and slow-onset formulation, in naïve and cocaine-sensitized mice.
  
  
  METHODS
  We investigated the development of sensitization after repeated administration of cocaine and cocaethylene and the effects of cocaethylene in animals previously exposed to cocaine. Cocaethylene was dissolved in two vehicles (saline and emulsion).
  
  
  RESULTS
  As observed with cocaine, chronic cocaethylene treatment in saline induced a behavioral sensitization, while in a sustained release emulsion, no behavioral sensitization was observed. Moreover, the expression of the sensitized behavior observed in cocaine-treated mice was reduced or totally abolished after cocaethylene administration in saline and emulsion, respectively. Interestingly, administration of cocaine in mice chronically treated with cocaethylene in saline induced an increase in locomotor activity as compared to control animals. In contrast, no difference was observed after the administration of cocaine in animals chronically treated with cocaethylene in emulsion or control group.
  
  
  CONCLUSIONS
  Cocaethylene in a sustained release emulsion blocked locomotor sensitization. These results suggest that cocaethylene, in a specific galenic preparation, such as gum, may be an efficacious harm-reduction alternative to cocaine users.
authors.affiliation: CNRS UMR7157, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Noble
authors.forename: Mario
authors.initials: M
authors.lastname: Sanchez
authors.forename: William
authors.initials: W
authors.lastname: Lowenstein
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003692:Delayed-Action Preparations; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004655:Emulsions; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D051379:Mice
chemical_list: D003692:Delayed-Action Preparations; D018765:Dopamine Uptake Inhibitors; D004655:Emulsions; C066444:cocaethylene; D003042:Cocaine