Chronic benzodiazepine administration. IX. Attenuation of alprazolam discontinuation effects by carbamazepine.
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 gamma-aminobutyric acidA (GABAA) 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 alprazolam administration. Treatment with carbamazepine attenuated (P less than 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.
Galpern
W R
WR
Department of Psychiatry, Tufts University School of Medicine, Boston MA.
Miller
L G
LG
Greenblatt
D J
DJ
Szabo
G K
GK
Browne
T R
TR
Shader
R I
RI
D000525:Alprazolam / Q000009:adverse effects*; D000818:Animals; D001007:Anxiety / Q000517:prevention & control*; D002220:Carbamazepine / Q000008:administration & dosage / Q000627:therapeutic use*; D002540:Cerebral Cortex / Q000378:metabolism; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D006624:Hippocampus / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D012640:Seizures / Q000517:prevention & control*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*; D013997:Time Factors
D011963:Receptors, GABA-A; D002220:Carbamazepine; D000525:Alprazolam