Evaluation of anxiolytic effect and withdrawal anxiety in chronic intermittent diazepam treatment in rats.
This study evaluated the effect of intermittent administration in the development of dependence to diazepam in chronic use of the drug. Gabapentin was used to provide an anxiolytic effect on drug-free days. During a 28-day treatment schedule, rats were given diazepam (15 mg/kg) once daily continuously, or intermittently with saline or gabapentin (50 mg/kg) on days 5, 10, 15, 20, and 25. Anxiety-like behavior was assessed on days 10 and 30 using the elevated plus-maze test and novelty-induced grooming test. Contrary to continuous administration, intermittent diazepam did not provide anxiolytic-like activity on day 10; instead, it prevented withdrawal anxiety on day 30. Gabapentin produced anxiolytic-like effects during the withdrawal period, but not on day 10. These results suggest that intermittent administration of diazepam (given either alone or alternatively with a drug possessing anxiolytic activity) may be of value in preventing the development of physical dependence during the chronic use of the drug. However, further studies are needed to demonstrate that this protocol could effectively produce anxiolytic activity on diazepam-free days.
Department of Pharmacology and Clinical Pharmacology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
Bariş
B
Açikmeşe
Seçil
S
Haznedar
Iclal
I
Hatipoğlu
Nurhan
N
Enginar
D000588:Amines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D001007:Anxiety / Q000139:chemically induced / Q000188:drug therapy*; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D003975:Diazepam / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004347:Drug Interactions; D000077206:Gabapentin; D006120:Grooming / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D000588:Amines; D014151:Anti-Anxiety Agents; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D003975:Diazepam