title: Lack of reinforcing effect of the benzodiazepine and tricyclic antidepressant combination of diazepam and dothiepin.
abstract: Fixed combinations of a tricyclic antidepressant (TCA) with a benzodiazepine (BZD) for the treatment of depressive syndromes enjoy remarkable acceptance among patients and prescribing physicians. In order to investigate if the widespread use of one such fixed TCA-BZD combination might be due to its high positive reinforcing effect, we tested each drug alone and in combination in an operant conditioning paradigm (fixed ratio 1 time-out 150 s) of intravenous self-administration in rats and compared their reinforcing effects to that of cocaine. Diazepam proved to be of only moderate reinforcing strength. Dothiepin alone was ineffective as a reinforcer but essentially abolished the reinforcing effect of diazepam when given in combination with it. These data indicate that the widespread acceptance of the fixed diazepam-dothiepin combination by the therapeutic community is not due to an increase in the positive reinforcing effect of diazepam by dothiepin but that, in contrast, addition of dothiepin might even decrease diazepam's moderately positive reinforcing effect.
authors.affiliation: Division of Neurochemistry, Department of Psychiatry, University of Innsbruck, Innsbruck, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Oittinen
authors.forename: H
authors.initials: H
authors.lastname: Rameis
authors.forename: A
authors.initials: A
authors.lastname: Saria
authors.forename: G
authors.initials: G
authors.lastname: Zernig
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D003975:Diazepam / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004308:Dothiepin / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D012646:Self Administration
chemical_list: D014151:Anti-Anxiety Agents; D000929:Antidepressive Agents, Tricyclic; D018765:Dopamine Uptake Inhibitors; D003042:Cocaine; D003975:Diazepam; D004308:Dothiepin