title: Effects of tiagabine and diazepam on operant ethanol self-administration in the rat.
abstract: 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.
authors.affiliation: Department of NEUROTEC, Karolinska Institute, Addiction Center South, Huddinge Hospital, Stockholm, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Rimondini
authors.forename: W
authors.initials: W
authors.lastname: Sommer
authors.forename: M
authors.initials: M
authors.lastname: Heilig
mesh_terms: 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
chemical_list: D002492:Central Nervous System Depressants; D018755:GABA Agonists; D018757:GABA Modulators; D009557:Nipecotic Acids; D000431:Ethanol; D003975:Diazepam; D000078308:Tiagabine