Negligible tolerance produced by chronic intravenous alprazolam administration: a low serum drug concentration effect

• Published in: Experimental and clinical psychopharmacology Vol. 9; no. 1; p. 110
• Main Authors: Lau, C E, Wang, Y, Sun, L, Falk, J L
• Format: Journal Article
• Language: English
• Published: United States 01.02.2001
• Subjects: Alprazolam - administration & dosage; Alprazolam - blood; Alprazolam - pharmacology; Animals; Anti-Anxiety Agents - administration & dosage; Anti-Anxiety Agents - blood; Anti-Anxiety Agents - pharmacology; Catheterization; Conditioning, Operant - drug effects; Dose-Response Relationship, Drug; Drug Tolerance; Infusions, Intravenous; Jugular Veins; Male; Rats; Rats, Sprague-Dawley; Reinforcement Schedule
• ISSN: 1064-1297
• DOI: 10.1037/1064-1297.9.1.110

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.