Antidepressants attenuate both the enhanced ethanol intake and ethanol-induced anxiolytic effects in diazepam withdrawn rats.
We have recently shown that the abrupt discontinuation of chronic diazepam (DZM) administration facilitated ethanol consumption and enhanced the anxiolytic properties of ethanol. Tricyclic antidepressants such as desipramine and the selective serotonin reuptake inhibitor fluoxetine have been shown to reduce alcohol intake in rodent models of alcoholism and in alcoholics who are depressed. In the present study, we tested whether desipramine (1.25; 2.5 and 5 mg/kg, i.p.) and fluoxetine (5 mg/kg, i.p.) treatment affect both ethanol intake in a free-choice test and the anxiolytic effect induced by ethanol in DZM withdrawn rats. Adult male Wistar rats were submitted to a chronic DZM treatment (2 mg/kg per day) or vehicle (VEH) for 21 days. Twenty-four hours after the last DZM injection, rats were subjected to a free-choice paradigm between water and increasing ethanol concentrations with or without concurrent desipramine or fluoxetine administration (ethanol concentration (v/v) was increased every 4 days as follows: 2, 4, 6, 8 and 10% for the final 8 days). Chronic treatment with desipramine (24 days, twice a day, 2.5 and 5 mg/kg, i.p.) and fluoxetine (24 days, once a day; 5 mg/kg, i.p.) significantly reduced the amount of ethanol intake in DZM withdrawn rats. Furthermore, subchronic treatments with desipramine (4 days, twice a day, 2.5 and 5 mg/kg) and fluoxetine (4 days, once a day, 5 mg/kg, i.p.) blocked the anxiolytic-like behavior in the elevated plus maze induced by ethanol (1 g/kg; i.p.) in DZM withdrawn rats at day 5 of withdrawal. The present findings suggest that desipramine and fluoxetine could be effective pharmacological tools to prevent the subsequent development of ethanol dependence in rats previously exposed to DZM withdrawal.
Martijena
Irene D
ID
Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, 5016 Córdoba, Argentina. imartije@fcq.unc.edu.ar
Bustos
Silvia G
SG
Bertotto
María E
ME
Molina
Víctor A
VA
D000428:Alcohol Drinking / Q000188:drug therapy* / Q000503:physiopathology; D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000009:adverse effects; D000928:Antidepressive Agents / Q000008:administration & dosage*; D001007:Anxiety / Q000139:chemically induced / Q000188:drug therapy*; D001522:Behavior, Animal; D002492:Central Nervous System Depressants / Q000009:adverse effects / Q000378:metabolism; D002755:Choice Behavior / Q000187:drug effects; D003891:Desipramine / Q000008:administration & dosage*; D003975:Diazepam / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D004334:Drug Administration Schedule; D004347:Drug Interactions; D000431:Ethanol / Q000009:adverse effects; D005473:Fluoxetine / Q000008:administration & dosage*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000209:etiology; D013997:Time Factors
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D002492:Central Nervous System Depressants; D005473:Fluoxetine; D000431:Ethanol; D003975:Diazepam; D003891:Desipramine