TY - JOUR
T1 - Acute administration of the GABA reuptake inhibitor tiagabine does not alter the effects of oral cocaine in humans
AU - Lile, Joshua A.
AU - Stoops, William W.
AU - Glaser, Paul E.A.
AU - Hays, Lon R.
AU - Rush, Craig R.
N1 - Funding Information:
We would like to thank Frances Wagner, R.N., Brad Coooper, Shelly Gray, Jamie Haga, Matt Weaver and Allison Weber for excellent medical and technical assistance. This research was supported by National Institute on Drug Abuse, grant DA 13567 awarded to Craig R. Rush; National Institute on Mental Health Training, grant MH 015730 awarded to Joshua A. Lile (trainee); and National Center for Research Resources, grant M01 RR02602 awarded to the General Clinical Research Center.
PY - 2004/10/5
Y1 - 2004/10/5
N2 - Drugs affecting central γ-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.
AB - Drugs affecting central γ-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.
KW - Cocaine
KW - Drug discrimination
KW - GABA
KW - Human
KW - Multiple-Choice Procedure
KW - Tiagabine
UR - http://www.scopus.com/inward/record.url?scp=5444241903&partnerID=8YFLogxK
U2 - 10.1016/j.drugalcdep.2004.04.010
DO - 10.1016/j.drugalcdep.2004.04.010
M3 - Article
C2 - 15380292
AN - SCOPUS:5444241903
SN - 0376-8716
VL - 76
SP - 81
EP - 91
JO - Drug and Alcohol Dependence
JF - Drug and Alcohol Dependence
IS - 1
ER -