We considered it appropriate to commence our studies with a formulation rather than with an individual herb because a formulation, comprising several ingredients, is more likely to contain a biologically useful chemical, and is therefore more likely to yield positive results. As the starting point for our research, we selected the most popular procognitive formulation (Mentat) marketed by the largest herbal pharmaceutical company (Himalaya Drug Company) in the country.

Mentat

Mentat is also known as BR-16A. It contains over 20 different ingredients; the exact formulation differs between pediatric and adult presentations of the composite. Important ingredients of BR-16A, suggested to improve memory function, include the following: Jal-brahmi (Bacopa monnieri), Mandookaparni (Centella asiatica), Ashwagandha (Withania somnifera), Shankapushpi (Evolvulus alsinoides), Jatamansi (Nardostachys jatamansi), Vach (Acorus calamus), Malkangni (Celastrus paniculatus), and Sonth (Zingiber officinale). Other ingredients of BR-16A, claimed to be "nerve tonics," include Tagar (Valeriana wallachii), Badam (Prunus amygdalus), Salap (Orchis mascula), Lavang (Syzygium aromaticum), and Pearl (Mukta pishti). The remaining ingredients are putative general tonics and vitalizers (Himalaya Drug Company, 1991).

We examined the cognitive benefits with Mentat (200 mg/kg/day) using a food-motivated paradigm in food-deprived rats studied in the Hebb-Williams complex maze and in the T maze. In the former task, each rat was trained to leave a start chamber, traverse corridors in the maze, and locate the reward chamber; the learning score was the time taken by the rat to reach the reward chamber. In the latter task, each rat was taught to leave the stem of the T maze, choose between correct and wrong arms of the maze, and locate the reward chamber at the end of the correct arm; the learning indices were the number of trials taken by the rat to achieve a criterion that defined satisfactory learning, and the number of wrong arm entries during this period.

The results were encouraging. We found that 3 weeks of administration of Mentat significantly improved Hebb-Williams maze learning in rats (Joseph et al., 1994). This established the potential of Mentat as a procognitive formulation worthy of examination in the context of ECT-induced cognitive dysfunction. We next showed that in an identical experimental design, Mentat attenuated anterograde amnestic deficits induced by six once-daily ECS (Joseph et al., 1994). In a second study, we found that rats that were pretrained in the Hebb-Williams and the T maze tasks, and which received six once-daily ECS, learned better during post-ECS reexposure to the same tasks if they had received Mentat for 2 weeks than if they had received placebo (Andrade et al., 1994a). It is uncertain, however, whether Mentat improved renewed learning, or enhanced retention of learning during the first (pre-ECS) exposure to the tasks, or both. In a third study, we found that the administration of Mentat for approximately I week to rats pretrained in the T maze resulted in an attenuation of the retrograde amnestic deficits induced by two ECS administered on the same day, 5 hours apart (Andrade et al., 1995). In the most elaborate study of all, we employed the Hebb-Williams maze to confirm that approximately 2 weeks of treatment with Mentat enhances the ability of rats to learn the task as well as attenuates both retrograde and anterograde amnesia induced by two once-daily ECS (Faruqi et al., 1995).

Results in healthy rats may not be generalizable to dysfunctional humans. In an attempt to make the animal model more representative of situations of clinical impairment, we preselected rats for poor learning on the Hebb-Williams maze and examined whether the administration of Mentat for 3 weeks could attenuate the anterograde amnestic effects of six once-daily ECS; the results again supported the use of Mentat (Ramteke et al., 1995).

We have not been able to offer any convincing explanation for the mechanism of procognitive action of Mentat. In only one of the studies described, we found that Mentat produced a small but statistically significant abbreviation of the ECS seizure duration (Faruqi et al., 1995). This finding was in line with unpublished data furnished by the drug company that Mentat shortens chemically induced seizures, and abbreviates breakthrough seizure duration in epileptic patients on antiepileptic medication. In this study, however, seizure duration showed no statistical relationship to the learning performance of the rats, suggesting that the mild anticonvulsant effect of Mentat did not directly or indirectly mediate its antiamnestic effects.

In another study, we used in vivo chemical challenges in rats to demonstrate that Mentat enhances dopamine postsynaptic receptor functioning, but does not influence the activity of dopamine autoreceptors or alpha-2 noradrenergic receptors (Andrade et al., 1994b). The relevance of these findings to the procognitive effects of Mentat requires further study.

Memorin

As already described, Mentat is a complex herbal formulation. With the expectation that not all of its contained ingredients are relevant to its procognitive actions, we searched for simpler formulations to study, and finally chose Memorin (Phyto-Pharma). This formulation is derived from Mandookaparni (Centella asiatica, Jatamansi (Nardostachys jatamansi), Yashtimadhu (Glycyrrhyza glabra), Shankapushpi (Evolvulus alsinoides), and a subformulation, Smruti Sagar. While Memorin is not exactly a subset of Mentat, there is considerable overlap in the contained ingredients.

We examined the cognitive benefits with Memorin (200 mg/kg/day), using the T maze as in the Mentat studies and using a passive avoidance paradigm. In the latter experiment, each rat was trained to remain in the bright chamber of a shuttle box to avoid receiving an electric shock in the dark chamber; the duration for which the rat remained in the bright chamber was its recall score.

As with Mentat, the results with Memorin were encouraging. The administration of Memorin for 2 weeks attenuated retrograde amnesia, measured using the passive avoidance paradigm, in rats that received two ECS on the same day, spaced 5 hours apart (Vinekar et al., 1998). Likewise, 2 weeks of Memorin attenuated the anterograde amnesia induced by two ECS (again administered on the same day, 5 hours apart) and measured in the T maze (Andrade et al., 1999). In neither study did Memorin influence the ECS seizure duration. As with Mentat, we were unable to suggest any mechanism for the procognitive action of Memorin.