Further evaluation of mechanisms associated with the antidepressant-like signature of scopolamine in mice.

Further evaluation of mechanisms associated with the antidepressant-like signature of scopolamine in mice. CNS Neurol Disord Drug Targets. 2017 Mar 09;: Authors: Martin AE, Schober DA, Nikolayev A, Tolstikov VV, Anderson WH, Higgs RE, Kuo MS, Laksmanan A, Catlow JT, Li X, Felder CC, Witkin JM Abstract Conventional antidepressants lack efficacy for many patients (treatment-resistant depression or TRD) and generally take weeks to produce full therapeutic response in others. Emerging data has identified certain drugs such as ketamine as rapidly-acting antidepressants for major depressive disorder and TRD. Scopolamine, a drug used to treat motion sickness and nausea, has also been demonstrated to function as a rapidly-acting antidepressant. The mechanisms associated with efficacy in TRD patients and rapid onset of action have been suggested to involve a-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and mammalian target of rapamycin (mTOR) signaling. Since the work on these mechanisms with scopolamine has been limited, the present set of experiments was designed to further explore these mechanisms of action. Male, NIH Swiss mice demonstrated a robust and immediate antidepressant signature when studied under the forced-swim test. The AMPA receptor antagonist NBQX prevented this antidepressant-like effect of scopolamine and ketamine. An orally-bioavilable mTOR inhibitor (ADZ8055) also attenuated the antidepressant-like ...
Source: CNS and Neurological Disorders Drug Targets - Category: Drugs & Pharmacology Authors: Tags: CNS Neurol Disord Drug Targets Source Type: research