title: Chronic low-dose alprazolam augments gamma-aminobutyric acid(A) receptor function.
abstract: After acute administration of low doses, alprazolam displays unusual behavioral and neurochemical characteristics. To determine whether chronic low-dose alprazolam has unique effects, we treated mice for 1-14 days with alprazolam 0.2 mg/kg per day and evaluated open-field activity, benzodiazepine receptor binding, t-butylbicyclophosphorothionate binding, and muscimol-stimulated chloride uptake. Open-field activity in treated mice was similar to that of control mice at each timepoint during alprazolam administration. Similarly, benzodiazepine receptor binding in vivo was unchanged in five brain regions. Benzodiazepine receptor binding in vivo was unchanged in five brain regions. Benzodiazepine binding in vitro in the cortex was unaffected by alprazolam treatment, as was t-butylbicyclophosphorothionate binding in the cortex. However, muscimol-stimulated chloride uptake was increased after 2 and 4 days of alprazolam compared with results after 1, 7, and 14 days. These results are consistent with prior reports of unusual effects of low-dose alprazolam and extend these findings to chronic administration.
authors.affiliation: Department of Pharmacology, Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: F
authors.initials: F
authors.lastname: Lopez
authors.forename: L G
authors.initials: LG
authors.lastname: Miller
authors.forename: D J
authors.initials: DJ
authors.lastname: Greenblatt
authors.forename: A
authors.initials: A
authors.lastname: Schatzki
authors.forename: M
authors.initials: M
authors.lastname: Lumpkin
authors.forename: R I
authors.initials: RI
authors.lastname: Shader
mesh_terms: D000525:Alprazolam / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001143:Arousal / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D015918:Infusion Pumps, Implantable; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000502:physiology
chemical_list: D011963:Receptors, GABA-A; D000525:Alprazolam