Negligible tolerance produced by chronic intravenous alprazolam administration: a low serum drug concentration effect.
In 3-hr sessions, the authors investigated the onset, peak, and disappearance of the effects of alprazolam on performance under a differential reinforcement of low rate 45-s schedule in rats. Alprazolam was administered chronically as a daily bolus dose (2 mg/kg) via the intravenous route. Alprazolam decreased the reinforcement rate and increased the shorter response (nonreinforced) rate in a dose- and time-related fashion. Tolerance did not develop to the decreases in reinforcement rate; tolerance to increases in shorter response rate was negligible, occurring only at the low-concentration range. Clinically, an optimal dose regimen should be designed to avoid the tolerance development that occurs in the low serum benzodiazepine concentration range.
Lau
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CE
Department of Psychology, Rutgers, The State University of New Jersey, Piscataway 08854-8020, USA. clau@rci.rutgers.edu
Wang
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Y
Sun
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Falk
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JL
D000525:Alprazolam / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D002404:Catheterization; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D007262:Infusions, Intravenous; D007601:Jugular Veins; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule
D014151:Anti-Anxiety Agents; D000525:Alprazolam