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 1% Tween 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 β1-selective adrenoceptor antagonist; propranolol, a non selective β-adrenoceptor antagonist; and prazocin, an α1-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 β2 receptors to produce an antidepressant action. Imipramine may act by activating β2 receptors by blocking or down-regulating β1 receptors.

Novel behavioral assays of spontaneous and precipitated THC withdrawal in mice

“…A plausible explanation for why non-cannabinoid drugs (i.e., mifepristone and propranolol) were ineffective is that the doses tested were simply insufficient to significantly affect withdrawal-induced behavior. However, dosing was based on published studies that demonstrated that these doses are sufficient to block the neuroendocrine stress response in mice (Al-tubuly et al, 2008; Chester et al, 2014; Kinsey et al, 2011; Lichtman et al, 2001). Thus, we speculate that THC withdrawal is a stressor that modulates the THC withdrawal-induced behaviors reported here, albeit not via catecholamine nor glucocorticoid receptors.…”

“…All drugs were dissolved in a vehicle composed of 5% ethanol, 5% Kolliphor EL (Sigma-Aldrich, St. Louis, MO), and 90% saline (Kinsey and Cole, 2013), with the exception of mifepristone, which was dissolved in a vehicle of 10% DMSO (Sigma-Aldrich), 10% TWEEN 80, and 80% saline. Doses and pretreatment times were chosen based on previous experience and literature (Al-tubuly et al, 2008; Chester et al, 2014; Kinsey et al, 2011; Lichtman et al, 2001). JZL184 (8 mg/kg, i.p.…”

Lifelong treatment with atenolol decreases membrane fatty acid unsaturation and oxidative stress in heart and skeletal muscle mitochondria and improves immunity and behavior, without changing mice longevity

“…The observed decrease in defecation and urination in Old-AT mice compared to Old controls indicates a lower anxiety status in these animals. These results agree with the decreases in anxiety (Deary et al ., 1991 ) and depression (Al-Tubuly et al ., 2008 ) reported after treatment with atenolol in human patients.…”

“…Although it is generally thought that immune cells have almost exclusively β-2 adrenergic receptors, there are results involving β-1 adrenergic receptor signaling in the modulation of immune responses (Emeny et al ., 2007 ), but their immunological relevance has been largely unexplored and the effect of atenolol on the immune cell functions has been scarcely studied. Concerning behavior, a few reports showed decreased anxiety (Deary et al ., 1991 ) and antidepressant effects (Al-Tubuly et al ., 2008 ) after atenolol treatment, but the impact of atenolol on behavioral parameters has not been investigated. In the case of the cardiovascular parameters, as an increase in mortality was detected only in very old individuals, the measurements were repeated at 35 months of age.…”

Anxiolytic- and antidepressant-like effects of an aqueous extract of Tanacetum parthenium L. Schultz-Bip (Asteraceae) in mice

“…Monoaminergic, serotoninergic, and noradrenergic systems are known to play major roles in major depression (Perona et al, 2008). However, the GABA system also participates in the antidepressant actions of thiazole-BDZ such as ALP that, in addition to enhancing the release of serotonin (5-HT) in the hippocampus to produce antidepressant actions, may act by means of a GABAergic mechanism that is independent of the BDZ-site receptor (Jonas and Cohon, 1993;Kalueff and Nutt, 2007;Al-Tubuly et al, 2008). Thus, as may be observed in Fig.…”