The Cannabinoid-Memory and the Angiotensin-Memory Paradoxes: Another Penrose Triangle?

Ramanujam N., MD .


This study aims to evaluate the efficacy of two different drugs in their effects on memory and discrimination learning in a dual, controlled mouse model of amnesia, and to relate the findings to their pharmacokinetic and pharmacodynamics profiles. It also aims at validating a sub-acute scopolamine dose protocol as a model of rodent amnesia, specifically of emotional memory.

The Exteroceptive models used include a Y-maze and an Elevated plus Maze (EPM). The Interoceptive models used are two different dose protocols of an amnesic drug, Scopolamine in forty-eight Swiss Albino mice, categorized into an acute and a sub-acute induction division, each of which later received fixed human equivalent doses of two drugs, apart from saline and scopolamine. Each animal was then evaluated for their Novelty Object Recognition (NOR) memory, and visuo-spatial memory, on the Y-maze and the EPM, respectively. The results of the Novelty Preference Test (NPT) and EPM test were analysed using Analysis of Variance.

The efficacy of Rimonabant in improving NOR memory was statistically higher than in saline and model control groups, more so in the acute induction. Its efficacy in enhancing visuo-spatial memory was less, although comparable to that on NOR memory.  The efficacy of Valsartan was lower than the NOR Recognition Indices of other groups, although insignificant statistically. Sub-acute induction resulted in increased amnesia and anxiety in the Valsartan group on both mazes, the former being comparable to that noted in scopolamine group.

Rimonabant is a memory enhancer, in terms of both recognition and spatial memory. Valsartan is a pro-amnesic drug in a sub-acute induction, in which it lead to increased anxiety additionally. Hence, sub acute scopolamine protocol could be a novel model of emotional memory. Though many drawbacks were noted in the study, the drug effects could be explained by pharmacokinetic data and pharmacodynamic effects. This pilot study could be used for correlating the results in human conditions involving memory.


Cannabinoid Receptor, Angiotensin Receptor, Rimonabant, Valsartan, acute Scopolamine amnesia, maze learning, novelty object recognition memory, spatial memory, sub-acute scopolamine amnesia, y-maze, elevated plus maze

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