A comparative study of the effect of supplementing citicoline with fluoxetine and amitriptyline on learning and memory in albino rats


  • Gramle Amol Department of Pharmacology, Sapthagiri Institute of Medical Sciences & Research Center, Bengaluru, Karnataka
  • Bhulan Prasad Loc Department of Pharmacology, Rajendra Institute of Medical Sciences, Ranchi, Jharkhand
  • Y. S. Ramya Department of Pharmacology, Bangalore Medical College and Research Institute, Bengaluru, Karnataka




, Antidepressants, Citicoline, Cognition


Background: The prevalence of psychosomatic complaints in children and adolescents has been reported to be between 10% and 25%. In addition, these problems present in a wide range of people across different age groups. Complaints of impaired learning and memory are common in patients treated with drugs acting on the central nervous system including the prototypical antidepressant drugs (AAD) such as fluoxetine and amitriptyline. Concomitant administration of the nootropic drug citicoline may help in the maintenance of cognition through the retention of memory and learning capacity.

Methods: Albino rats were used for this study as they are the most standardized of all experimental animals and divided into five groups of six rats each including the control group. The test apparatus used was the Morris water maze which is one of the most widely used tasks in behavioral neuroscience for studying the psychological processes and neural mechanisms of spatial learning and memory. The drugs used in the study were fluoxetine amitriptyline and citicoline. All the rats received respective treatment for the period of 20 days. The experiment was conducted during the last week. During this period, the rats were simultaneously trained and tested for 4 days for learning behavior (i.e. from 14th to 17th day of the study) designated as day 1, day 2, day 3, and day 4. After a gap of 2 days, i.e. on day 20, the rats were tested for the retention of memory on Morris water maze (designated as day 6).

Results: There was a statistically significant impairment in learning behavior of the rats in fluoxetine and amitriptyline group when compared to control group (p<0.01 is highly significant) but no such significance was obtained when the groups containing the AADs was supplemented with citicoline. In addition, fluoxetine caused more impairment than amitriptyline and supplemental citicoline was beneficial in retaining the memory and preventing learning impairment, but the combination is more beneficial in the amitriptyline group as compared to the fluoxetine group.

Conclusions: Cognition in individuals with depression may be influenced by several factors, including basic neuropathology and the frequency and severity of depressive episodes. The major finding of the present study is that learning was impaired by both the antidepressants, i.e., fluoxetine and amitriptyline but was reversed by citicoline which has a novel mechanism of action.


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How to Cite

Amol, G., Loc, B. P., & Ramya, Y. S. (2016). A comparative study of the effect of supplementing citicoline with fluoxetine and amitriptyline on learning and memory in albino rats. International Journal of Basic & Clinical Pharmacology, 4(5), 884–887. https://doi.org/10.18203/2319-2003.ijbcp20150860



Original Research Articles