Slow response to the standard treatment for depression increases suffering and risk of suicide. Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, can rapidly alleviate depressive symptoms and reduce suicidality, possibly by decreasing hyperactivity in the lateral habenula (LHb) brain nucleus. Here we find that in a rat model of human depression, opioid antagonists abolish the ability of ketamine to reduce the depression-like behavioral and LHb hyperactive cellular phenotypes. However, activation of opiate receptors alone is not sufficient to produce ketamine-like effects, nor does ketamine mimic the hedonic effects of an opiate, indicating that the opioid system does not mediate the actions of ketamine but rather is permissive. Thus, ketamine does not act as an opiate but its effects require both NMDA and opiate receptor signaling, suggesting that interactions between these two neurotransmitter systems are necessary to achieve an antidepressant effect.

No abstract

No abstract

Background:We had previously demonstrated that a complex herbal formulation (Mentat; Himalaya Drug Company, Bangalore) attenuated anterograde and retrograde amnesia induced by electroconvulsive shocks (ECS) in rats. We later showed that a simplified formulation (Memorin; Phyto Pharma, Kolhapur) had similar effects.Aims:In an attempt to identify the ingredients (of the complex formulation), which purveyed the cognitive benefits, we studied two of the constituent herbs, Brahmi and Mandookaparni, separately and together. The experiments included both active (piracetam) and inactive (vehicle) controls.Methods:Adult, male, Sprague–Dawley rats (n=8 per group) were randomized to receive Brahmi, Mandookaparni, a combination of these two herbs (A300), piracetam, or vehicle from days 1 to 15. On days 11 and 12, the rats were trained in a T-maze using a food-driven paradigm. On days 13 and 14, half the rats in each group received 2 ECS (60 mC charge) per day, 5 hours apart. On day 15, recall of pre-ECS learning was assessed. On day 16, transfer of learning was assessed.Results:None of the active treatments facilitated pre-ECS learning or influenced ECS seizure duration; however, all showed varying but generally favourable profiles in the attenuation of ECS-induced retrograde and anterograde amnesia. The combination of Brahmi and Mandookaparni showed no especial advantage over the individual herbs.Conclusion:Brahmi and Mandookparni do not in themselves improve learning; however, each attenuates the amnestic effects of ECS without showing synergism in this beneficial action. Exercises in research and development are indicated to further investigate the anti-amnestic properties of these herbs, and to identify the specific chemical constituents which have procognitive effects.