Effects of tiagabine and diazepam on operant ethanol self-administration in the rat.
OBJECTIVE
Benzodiazepines (BDZ) are widely used in the treatment of anxiety and ethanol withdrawal. It has been suggested that this class of compounds may increase the reinforcing value of ethanol; however, the literature is scarce. Tiagabine has recently been introduced into clinical use as an anti-epileptic drug. It acts through inhibiting gamma-aminobutyric acid (GABA) reuptake, and thus represents a pharmacodynamically novel principle for potentiating GABAergic transmission. The objective of the present study was to examine whether these two manners of modulating GABAergic transmission would affect ethanol self-administration in rats.


METHODS
Rats were trained on an operant oral ethanol self-administration task in a two-lever free-choice paradigm. When trained, subjects were treated with tiagabine (2, 6 and 18 mg/kg, intraperitoneally [i.p.]) or diazepam (0.5, 1.5 and 4.5 mg/kg, i.p.). Postsession blood alcohol concentrations and locomotor activity measures also were obtained.


RESULTS
At nonsedating doses, neither tiagabine nor diazepam affected operant ethanol self-administration. At the highest doses (18 and 4.5 mg/kg, respectively), both drugs suppressed ethanol self-administration but also induced significant suppression of locomotion, indicative of sedation.


CONCLUSIONS
Systemic administration of either the GABA-uptake blocker, tiagabine, or the GABA/BDZ agonist, diazepam, at nonsedating doses does not seem to affect oral ethanol self-administration.
Rimondini
R
R
Department of NEUROTEC, Karolinska Institute, Addiction Center South, Huddinge Hospital, Stockholm, Sweden.
Sommer
W
W
Heilig
M
M
D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D018755:GABA Agonists / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009557:Nipecotic Acids / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration / Q000706:statistics & numerical data; D000078308:Tiagabine
D002492:Central Nervous System Depressants; D018755:GABA Agonists; D018757:GABA Modulators; D009557:Nipecotic Acids; D000431:Ethanol; D003975:Diazepam; D000078308:Tiagabine