MK-801 and enantiomers: Potential antidepressants or false positives in classical screening models?

NMDA receptor/nitrergic system blockage augments antidepressant-like effects of paroxetine in the mouse forced swimming test

“…Postmortem studies in depression also revealed changes in high-affinity glycine binding to the NMDA receptor in the frontal cortex of suicide victims (Nowak et al 1995) and the principal subunit for the NMDA receptor, NMDAR1, in the hippocampus (Law and Deakin 2001). Moreover, many studies have reported antidepressant-like effects of a variety of NMDA receptor antagonists in animal models of depression such as the mouse FST (Almeida et al 2006a, b;Layer et al 1995;Maj et al 1992a;Rosa et al 2003;Trullas et al 1991;Trullas and Skolnick 1990) and TST (Kos and Popik 2005;Panconi et al 1993;Trullas and Skolnick 1990). On the other hand, depressed patients have been reported to have increased plasma levels of nitrate, the end product of NO metabolism, suggesting that NO production is increased in depression (Suzuki et al 2001).…”

Behavioral analysis during the forced swimming test using a joystick device

“…Tricyclic antidepressants, monoamine oxidase inhibitors, and atypical antidepressants such as mianserine and iprindole, are all effective in this paradigm (Borsini and Meli, 1988). However, there are several shortcomings with the traditional type of measurement and several compounds have been recognized as false positive (Borsini and Meli, 1988;Delini-Stula et al, 1988;Panconi et al, 1993) or negative (Lucki, 1997). In his original paper Porsolt describe the immobility posture as those movements necessary only to keep the animal's head above the water (Porsolt et al, 1977).…”

Early behavioral screening for antidepressants and anxiolytics

“…In our hands, the mouse version appears somewhat more sensitive to uptake inhibitors. The weak but significant activity of nicotine at 1 mg/kg is consistent with the fact that excitatory substances may constitute false-positives in the behavioral despair test [Porsolt et al, 1978a,b;Panconi et al, 1993]. Nevertheless, antidepressant-like activity of nicotine has also been described in the mouse [Suemaru et al, 2006] and in the rat [Vazquez-Palacios et al, 2004].…”