The Effect of Sympathetic Antagonists on the Antidepressant Action of Alprazolam

ABSTRACT

Alprazolam is an anti-anxiety drug shown to be effective in the treatment of depression. In this study; the effect of sympathetic receptor antagonists on alprazolam-induced antidepressant action was studied using a mouse model of forced swimming behavioral despair. The interaction of three sympathetic receptor antagonists with benzodiazepines; which may impact the clinical use of alprazolam; was also studied. Behavioral despair was examined in six groups of albino mice. Drugs were administered intraperitoneally. The control group received only a single dose of 1Tween 80. The second group received a single dose of alprazolam; and the third group received an antagonist followed by alprazolam. The fourth group was treated with imipramine; and the fifth group received an antagonist followed by imipramine. The sixth group was treated with a single dose of an antagonist alone (atenolol; a Beta1-selective adrenoceptor antagonist; propranolol; a non selective Beta-adrenoceptor antagonist; and prazocin; an a1-adrenoceptor antagonist). Results confirmed the antidepressant action of alprazolam and imipramine. Prazocin treatment alone produced depression; but it significantly potentiated the antidepressant actions of imipramine and alprazolam. Atenolol alone produced an antidepressant effect and potentiated the antidepressant action of alprazolam. Propranolol treatment alone produced depression; and antagonized the effects of alprazolam and imipramine; even producing depression in combined treatments. In conclusion; our results reveal that alprazolam may produce antidepressant effects through the release of noradrenaline; which stimulates Beta2 receptors to produce an antidepressant action. Imipramine may act by activating Beta2 receptors by blocking or down-regulating Beta1 receptors