title: Acute administration of the GABA reuptake inhibitor tiagabine does not alter the effects of oral cocaine in humans.
abstract: Drugs affecting central gamma-aminobutyric acid (GABA) systems may have promise as treatments for cocaine addiction. In the present study, tiagabine (Gabatril), a GABA reuptake inhibitor, was investigated for its ability to modify the discriminative-stimulus, reinforcing, subject-rated, performance and cardiovascular effects of oral cocaine in non-treatment seeking cocaine users. Initially, acute doses of 4 mg tiagabine were tested alone and in combination with oral cocaine in four participants to establish the safety of cocaine-tiagabine combinations. A higher dose of tiagabine (8 mg) was then tested in a larger group (n = 6). Participants learned to discriminate 150 mg of oral cocaine. The effects of cocaine (0-150 mg, p.o.) administered alone and in combination with tiagabine were then determined. Subject-rated, performance and cardiovascular measures were obtained at regular intervals. The reinforcing effects of cocaine, tiagabine and cocaine-tiagabine combinations were assessed using the Multiple-Choice Procedure. Cocaine alone produced prototypical behavioral and physiological effects (i.e., functioned as a discriminative and reinforcing stimulus, produced stimulant-like subject-rated effects, improved performance and increased heart rate). In general, acute administration of tiagabine did not alter the effects of oral cocaine. These findings suggest that tiagabine would not be effective at preventing continued cocaine use by blocking its acute, abuse-related effects.
authors.affiliation: Department of Behavioral Science, College of Medicine, University of Kentucky, College of Medicine Office Building (Room No. 127), Lexington, KY 40536-0086, USA.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Lile
authors.forename: William W
authors.initials: WW
authors.lastname: Stoops
authors.forename: Paul E A
authors.initials: PE
authors.lastname: Glaser
authors.forename: Lon R
authors.initials: LR
authors.lastname: Hays
authors.forename: Craig R
authors.initials: CR
authors.lastname: Rush
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D003042:Cocaine / Q000008:administration & dosage*; D004192:Discrimination, Psychological / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006801:Humans; D008875:Middle Aged; D014179:Neurotransmitter Uptake Inhibitors / Q000008:administration & dosage*; D009557:Nipecotic Acids / Q000008:administration & dosage*; D000078308:Tiagabine; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D004338:Drug Combinations; D014179:Neurotransmitter Uptake Inhibitors; D009557:Nipecotic Acids; D005680:gamma-Aminobutyric Acid; D003042:Cocaine; D000078308:Tiagabine