title: Comparative Evaluation of Partial α2 -Adrenoceptor Agonist and Pure α2 -Adrenoceptor Antagonist on the Behavioural Symptoms of Withdrawal after Chronic Alcohol Administration in Mice.
abstract: As an addictive drug, alcohol produces withdrawal symptoms if discontinued abruptly after chronic use. Clonidine (CLN), a partial α2 -adrenergic agonist, and mirtazapine (MRT), an antagonist of α2 -adrenoceptor, both clinically aid alcohol withdrawal. Considering different mechanisms of action of the two drugs, this study was designed to see how far these two mechanistically different drugs differ in their ability to decrease the severity of ethanol withdrawal syndrome. The effect of CLN and MRT on ethanol withdrawal-induced anxiety, depression and memory impairment was analysed using EPM, FST and PAR tests, respectively. Animals received distilled water, ethanol and/or either of the drugs (CLN and MRT) in different doses. Relapse to alcohol use was analysed by CPP test. Animals received ethanol as a conditioning drug and distilled water, CLN or MRT as test drug. CLN and MRT both alleviated anxiety in a dose-dependent manner. MRT (4 mg/kg) was more effective than CLN (0.1 mg/kg) in ameliorating the anxiogenic effect of alcohol withdrawal. However, CLN treatment increased depression. It significantly decreased swimming time and increased immobility time, whereas MRT treatment decreased immobility time and increased climbing and swimming time during abstinence. The effect was dose dependent for both drugs. The results of PAR test show that CLN treatment worsens working memory. Significant increase in SDE and TSZ and decrease in SDL were observed in CLN-treated animals. MRT treatment, on the other hand, improved working memory at both doses. Further, both CLN and MRT alleviated craving. A significant decrease in time spent in the ethanol-paired chamber was seen. MRT treatment at both doses showed better effect than CLN in preventing the development of preference in CPP test. These findings indicate a potential therapeutic use and better profile of mirtazapine over clonidine in improving memory, as well as in alleviating depression, anxiety and craving associated with alcohol withdrawal.
authors: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard University, New Delhi, India.
authors: Shivani
authors: S
authors: Arora
authors: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard University, New Delhi, India.
authors: Divya
authors: D
authors: Vohora
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000437:Alcoholism / Q000175:diagnosis / Q000188:drug therapy*; D000818:Animals; D001007:Anxiety / Q000188:drug therapy; D001522:Behavior, Animal / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D003863:Depression / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D008297:Male; D008568:Memory / Q000187:drug effects; D008803:Mianserin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D000078785:Mirtazapine; D011941:Receptors, Adrenergic / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000175:diagnosis / Q000188:drug therapy*
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000317:Adrenergic alpha-Antagonists; D011941:Receptors, Adrenergic; D008803:Mianserin; D000078785:Mirtazapine; D003000:Clonidine