Altered behavioral and neurochemical response to stress in benzodiazepine-withdrawn rats.
Rats chronically treated with diazepam (DZM) (2 mg/kg/day i.p.) for 21 days, were subsequently tested at 24, 48, 72 and 96 h after the last injection in the elevated plus-maze. When compared with their respective controls, withdrawn animals showed an anxiogenic response since they exhibited a significant decrease in the % of time spent in the open arms, and a reduction in open and total arms entries at 24 and 48 h following the last benzodiazepine administration. No other behavioral differences were observed in the remaining groups. Ninety-six hours following DZM withdrawal, when the anxiogenic response was no longer evident, withdrawn rats showed a significant decrease in immobility time when exposed to a forced-swim test (FST). GABA stimulation of chloride uptake in cortical tissue was measured in BDZ-withdrawn rats or vehicle-treated animals with or without exposure to the FST. An enhanced chloride uptake following GABA stimulation was observed in vehicle-treated rats following the swimming trial. However, similar values of chloride uptake were found among rats withdrawn from DZM at 96 h either exposed or not to the FST and vehicle-treated animals without prior stress exposure. These findings show that BDZ withdrawal alters the neurochemical and behavioral response to a subsequent stressful experience. These lines of evidence may indicate that BZD withdrawal reduced the ability to develop an adaptive response to stress.
Martijena
I D
ID
Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina.
Tapia
M
M
Molina
V A
VA
D000818:Animals; D014151:Anti-Anxiety Agents / Q000009:adverse effects*; D001007:Anxiety / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D018118:Chloride Channels / Q000378:metabolism; D002713:Chlorine; D003975:Diazepam / Q000009:adverse effects; D008297:Male; D011868:Radioisotopes; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000378:metabolism* / Q000523:psychology*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism* / Q000523:psychology*; D013550:Swimming; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D018118:Chloride Channels; D011868:Radioisotopes; D002713:Chlorine; D005680:gamma-Aminobutyric Acid; D003975:Diazepam