Noise stress and the development of benzodiazepine dependence in the rat.
Rats housed in conditions of noise stress were given daily injections of diazepam (4 mg/kg). Significant tolerance developed to the sedative effects within 5 days of treatment, as measured by head dipping and motor activity in the holeboard and by the number of closed arm entries in the plus-maze. These results are in agreement with other reports of rapid tolerance to sedative effects. However, in contrast to the usual finding of tolerance to anxiolytic actions after 2-3 weeks of treatment, in this study no tolerance developed after 23 days of treatment to diazepam's anxiolytic effects in the plus-maze. On withdrawal from the 23 days of diazepam treatment, there was no anxiogenic response in the plus-maze. Therefore, it seems that when chronic administration of diazepam is accompanied by chronic stress, tolerance does not occur to the anxiolytic effects, although it does develop to the sedative effects.
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Psychopharmacology Research Unit, UMDS Division of Pharmacology, Guy's Hospital, London, United Kingdom.
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D000818:Animals; D014151:Anti-Anxiety Agents; D001143:Arousal / Q000187:drug effects*; D003975:Diazepam; D004361:Drug Tolerance; D005106:Exploratory Behavior / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009622:Noise / Q000009:adverse effects*; D051381:Rats; D013315:Stress, Psychological / Q000150:complications*; D019966:Substance-Related Disorders / Q000523:psychology*
D014151:Anti-Anxiety Agents; D003975:Diazepam