Memory Consolidation

Abstract     

Propranolol is a beta adrenergic blocker that treats cardiovascular diagnoses, but it has certain side effects. Propranolol’s effect on memory has been a researched topic. In this experiment we analyze propranolol’s effect on memory consolidation of rats by comparing training and retention latencies in an inhibitory avoidance experiment. Our data showed no significant difference in retention of training latencies in propranolol injected rats. Rats injected with propranolol did not decrease their training latency, so there was no inhibitory effect of propranolol on memory consolidation in our rats. This did not support the notion that the drug could be used to treat hyperactive memory consolidation for patients with related psychiatric disorders such as post traumatic stress disorder, however further studies can be conducted with variant methods and dosages. 

Introduction

Propranolol is an adrenaline and noradrenaline antagonist and works by binding to multiple receptors to block the sympathetic nervous system. It is commonly used for the treatment of hypertension, heart attacks, and cardiomyopathy. This makes the drug effective in many cases that deal with the noradrenergic system. The noradrenergic system within the basolateral amygdala is a primal enhancer of memory consolidation (Pigeon et al., 2022). Consolidation of memory defines the process of short term memory turning into stored long term memory. Due to its strengthening effect on emotional memory, the noradrenergic system plays a big role in the pathophysiology of post traumatic stress disorder (PTSD) . During a trauma event, the hyperactivation of the sympathetic system can cause over consolidation of the memory (Lonergan et al., 2013). Over consolidation due to a hyperactive amygdala and sympathetic system can give way to rapid memory triggering from traumatic memories, thus resulting in an emotional disorder like PTSD. As an inhibitor for these core mechanisms, propranolol could be an essential treatment.

Along with the rush of endogenous hormones, protein synthesis is also needed within the amygdala for consolidation (Lonergan et al., 2013). Propranolol has been shown to be an effective inhibitor of the noradrenergic system and protein synthesis (Lonergan et al., 2013). To experiment with propranolol’s effects on rats’ memory consolidation, we conducted an inhibitory avoidance study, and measured training and retention latencies. A higher retention latency would indicate increased consolidation. Since propranolol is an effective inhibitor, we hypothesized that the drug injected rats would show lower retention latencies than the control (saline) group.

Methods

Subjects and Drugs

         Rats used were 18 male Envigo Sprague Dawleys. They weighed in at an average 388.125 +/- 17.496 grams. Rats were kept in pairs with food and water readily available. They were kept in housing with low lighting. All rats were handled and experimented on in compliance with the Institutional Animal Care and Use Committee at the University of Texas at Dallas.   For the test group, propranolol was dosed at 20mg per kg body weight and the control group received an equivalent volume of normal saline.

Procedure

         The inhibitory avoidance experiment was a 2 week experiment, where the first week was for the record of training latency, and the second week was the observation of retention latency. The set up of the experiment consisted of a two chamber alleyway with a light and dark compartment, and a shut door in between. The experiment room was dimly lit and minimal noise levels were maintained. Each rat was placed in the light chamber, facing away from the dark chamber. The time it took for the rat to turn around and enter the dark chamber on all four paws was recorded, and the door was closed once the rat completely crossed over. This represented the training latency. Then when the rat turned around with all four paws on the floor, it was administered a 1 second 0.5 mA shock in the dark chamber. After ten seconds, the rat was removed and given an intraperitoneal injection of propranolol or saline. The rat was then placed in a cage separate from the rats not yet tested. This was done to all 16 subject rats. The chambers were sanitized with 70% ethanol between each rat.

         One week later, the rats were placed in the same double chamber apparatus following the same procedures, omitting the shocks. During this round, the time recorded represented the rats’ retention latency, with a maximum of 10 minutes. After the ten minutes, the rat was removed and placed back to its original cage.

Statistical Analysis

         The mean results of the 18 rats were calculated along with a standard error.  The collected data was analyzed using a two sample T- Test with assumed equal variances. For statistical significance, p<0.05 was used.

Results

         The results were gathered after all 18 rats were experimented in the IA apparatus, at the end of the 2 weeks. The results for the first week, which consisted of data gathered for training latencies showed no significant difference between the rats that would be injected with propranolol and the rats that would be injected with saline ( 7.9744 +/- 1.11768 vs 6.9166 +/- 1.3776, p=0.5794 fig. 1a). Retention latency data collected in the second week also showed no significant difference between the propranolol injected rats and the saline injected rats (307.811 +/- 93.219 vs. 274.931 +/- 97.5851 p=0.8235 fig. 1b).

Discussion

         Earlier experiments testing propranolol’s therapeutic effect on emotional memory have been a mix of results. Some experiments yielded supportive data, while others have showed no significance. Like the one Stegeren and colleagues performed in 2005, propranolol showed a significant disruption of emotional material memory consolidation within humans (Stegeren et al. 2005), contradicting our results in our experiment. Compared to a placebo, propranolol decreased amygdala activation in test subjects that were exposed to emotional pictures (Stegeren et al. 2005). Consequently, in the 2014 experiment done by Bos and Beckers, propranolol was unsuccessful in inhibiting conditioned fear response following a three day conditioning period (Bos et al. 2014), which was consistent with our findings. These results and many more are relatively contradictory, so a definitive conclusion about the drug cannot be made. Further research can be done using different dosages and supplemental factors. Our experiment was done using around 8 mg, so a higher dosage might yield different results. Our inhibitory avoidance experiment was a step forward in the research of propranolol’s effects on memory, but it did not give us significant supporting data. However, based on some of the supportive results, propranolol may have the potential to be an effective drug in the treatment of memory consolidation disorders.