Details

Autor(en) / Beteiligte

• Galpern, Wendy R.
• Miller, Lawrence G.
• greenblatt, David J.
• Szabo, George K.
• Browne, Thomas R.
• Shader, Richard I.

Titel

Chronic benzodiazepine administration: IX. Attenuation of alprazolam discontinuation effects by carbamazepine

Ist Teil von

• Biochemical pharmacology, 1991-12, Vol.42, p.S99-S104

Ort / Verlag

New York, NY: Elsevier Inc

Erscheinungsjahr

1991

Quelle

Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)

Beschreibungen/Notizen

• Clinical studies suggest that carbamazepine may attenuate effects of alprazolam discontinuation. Since discontinuation of chronic alprazolam in a mouse model is associated with behavioral alterations and upregulation at the y-aminobutyric acid A (GABA A) receptor, we studied the effects of carbamazepine administration after alprazolam (2 mg/kg/day) discontinuation. Open-field activity was increased in mice 4 days after alprazolam discontinuation, but this effect was reduced significantly by continuous infusion of carbamazepine, 25 or 100 mg/kg/day. Benzodiazepine receptor binding in vivo was increased in cortex at 2 and 4 days after alprazolam discontinuation, and in hypothalamus at 4 days; with carbamazepine, 100 mg/kg/day, binding in both regions at these time points was similar to control values. Similar results were observed in cortex with benzodiazepine receptor binding in vitro. GABA-dependent chloride uptake was also increased at 4 days after alprazolam administration. Treatment with carbamazepine attenuated (P < 0.10) this increase. Carbamazepine alone after vehicle did not alter benzodiazepine binding or GABA-dependent chloride uptake. These results indicate that carbamazepine administration after alprazolam discontinuation attenuates behavioral and neurochemical alterations associated with discontinuation.