Comparison of zolpidem and midazolam self-administration under progressive-ratio schedules: consumer demand and labor supply analyses.
Progressive ratio (PR) schedules of intravenous drug self-administration are useful for establishing the relationships between reinforcing effectiveness and pharmacological actions of abused drugs. The authors compared the reinforcing effects of 2 short-duration benzodiazepine-type drugs differing in their receptor selectivity: zolpidem (selective for gamma aminobutyric acid Type A [GABA(A)] receptors containing alpha1 subunits) and midazolam (nonselective). Reinforcing effectiveness was evaluated using a PR schedule of intravenous drug injection in rhesus monkeys in which the response requirement increased across the experimental session and the initial response requirement (IRR) was varied. Analyses based on consumer demand and labor supply models of behavioral economics revealed that the relative reinforcing effectiveness of zolpidem was greater than that of midazolam. For consumer demand analyses, the degree of difference between zolpidem and midazolam depended on whether price was calculated on the basis of different IRRs or different doses of drug. According to labor supply analysis, the reinforcing effects of midazolam were influenced by the economic concept referred to as a price effect to a greater degree than those of zolpidem. These findings suggest that a compound with selectivity for GABA(A) receptors containing alpha1 subunits has greater reinforcing effectiveness than a nonselective compound with similar pharmacokinetics, albeit under a limited range of conditions (high response costs). Differences in price effects may play a key role in determining the relative reinforcing effectiveness of selective versus nonselective benzodiazepine agonists.
Rowlett
James K
JK
Harvard Medical School, New England Primate Research Center, Southborough, MA 01772, USA. james_rowlett@hms.harvard.edu
Lelas
Snjezana
S
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule / Q000662:veterinary; D005260:Female; D006993:Hypnotics and Sedatives / Q000008:administration & dosage*; D007275:Injections, Intravenous; D008253:Macaca mulatta; D008297:Male; D008874:Midazolam / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage*; D012055:Reinforcement Schedule; D012646:Self Administration / Q000191:economics / Q000379:methods / Q000523:psychology; D000077334:Zolpidem
D006993:Hypnotics and Sedatives; D011725:Pyridines; D000077334:Zolpidem; D008874:Midazolam