TY - JOUR
T1 - Low-dose alprazolam augments motor activity in mice
AU - Lopez, Fred
AU - Miller, Lawrence G.
AU - Greenblatt, David J.
AU - Paul, Steven M.
AU - Shader, Richard I.
PY - 1988/6
Y1 - 1988/6
N2 - The triazolobenzodiazepine alprazolam appears to have a unique clinical spectrum, and recent studies indicate unusual binding properties at the benzodiazepine receptor when assessed in vivo at low doses (0.02-0.05 mg/kg). To assess the behavioral activity of alprazolam at low doses, we examined open-field activity after one hour in mice treated with alprazolam, triazolam, and clonazepam. Following triazolam and clonazepam administration, open-field activity decreased in a dose-dependent fashion. In contrast, low doses of alprazolam resulted in an increase in open-field activity, whereas higher doses decreased activity. For all three drugs, activity was linearly related to receptor binding. Pretreatment with a dose of the benzodiazepine antagonist Ro15-1788 sufficient to fully occupy receptors had no effect on open-field activity, but when administered concurrently with alprazolam (0.05 mg/kg) prevented the increase in activity seen with alprazolam alone. Increased open-field motor activity represents a behavioral correlate to the increases in receptor binding seen with low-doses of alprazolam. Changes in activity appear to be mediated at the benzodiazepine receptor, since an antagonist prevents increased activity. These data suggest that the unique clinical effects of alprazolam may be due in part to unusual interactions with the benzodiazepine receptor.
AB - The triazolobenzodiazepine alprazolam appears to have a unique clinical spectrum, and recent studies indicate unusual binding properties at the benzodiazepine receptor when assessed in vivo at low doses (0.02-0.05 mg/kg). To assess the behavioral activity of alprazolam at low doses, we examined open-field activity after one hour in mice treated with alprazolam, triazolam, and clonazepam. Following triazolam and clonazepam administration, open-field activity decreased in a dose-dependent fashion. In contrast, low doses of alprazolam resulted in an increase in open-field activity, whereas higher doses decreased activity. For all three drugs, activity was linearly related to receptor binding. Pretreatment with a dose of the benzodiazepine antagonist Ro15-1788 sufficient to fully occupy receptors had no effect on open-field activity, but when administered concurrently with alprazolam (0.05 mg/kg) prevented the increase in activity seen with alprazolam alone. Increased open-field motor activity represents a behavioral correlate to the increases in receptor binding seen with low-doses of alprazolam. Changes in activity appear to be mediated at the benzodiazepine receptor, since an antagonist prevents increased activity. These data suggest that the unique clinical effects of alprazolam may be due in part to unusual interactions with the benzodiazepine receptor.
KW - Alprazolam
KW - Benzodiazepine
KW - Open-field
KW - Triazolam
UR - http://www.scopus.com/inward/record.url?scp=0024157753&partnerID=8YFLogxK
U2 - 10.1016/0091-3057(88)90488-1
DO - 10.1016/0091-3057(88)90488-1
M3 - Article
C2 - 2845448
AN - SCOPUS:0024157753
SN - 0091-3057
VL - 30
SP - 511
EP - 513
JO - Pharmacology, Biochemistry and Behavior
JF - Pharmacology, Biochemistry and Behavior
IS - 2
ER -