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Year : 1998  |  Volume : 30  |  Issue : 4  |  Page : 267-270

Study of neuro-excitatory features during diazepam-withdrawal reactions and their correlation with brain gamma-aminobutyric acid levels

Correspondence Address:
Singh Hardyal

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Source of Support: None, Conflict of Interest: None

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Objective: To evaluate the various neuro-excitatory components of diazepam (DZP) withdrawal reactions and to correlate them with the brain levels of Gamma-Aminobutyrlc Acid(GABA). Methods: Diazepam withdrawal reactions were produced in rats by abrupt cessation of continued ascending doses of DZP viz 10,12,14,16,18 mg/ kg, twice a day, given for 5 days. Neuro-excitatory features were indicated by a fall in sleeping time and pain threshold and a rise in halothane need and behavioural index. The test groups received normal saline, clonidine 62.5 'g/kg or propranolol 10 mg/kg. Groups with continued DZP administration with or without abrupt cessation served as references for comparison. Brain GABA levels were estimated to establish correlation (if any) with the aforesaid experimental observations. Results: Abrupt DZP cessation after continued use evoked neuro-excitation and produced rise in behavioural index, halothane need and a fall in sleeping time, and in GABA levels in hypothalamus, corpusstrlatum and cerebellum. These changes were reversed by clonidlne or propranofol pretreatment. Conclusion: The study reveals that sudden stoppage of continued use of DZP produces withdrawal reactions. Fall in brain GABA levels confirms neuro-excitation. Clonidlne and propranold, inhibitors of central adrenergic outflow, reverse these changes.


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