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Link to original content: http://pubmed.ncbi.nlm.nih.gov/36986498/
Potential Anti-Amnesic Activity of a Novel Multimodal Derivative of Salicylamide, JJGW08, in Mice - PubMed Skip to main page content
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. 2023 Mar 6;16(3):399.
doi: 10.3390/ph16030399.

Potential Anti-Amnesic Activity of a Novel Multimodal Derivative of Salicylamide, JJGW08, in Mice

Elżbieta Żmudzka  1 , Klaudia Lustyk  2 , Kinga Sałaciak  2 , Agata Siwek  3 , Jolanta Jaśkowska  4 , Marcin Kołaczkowski  5 , Jacek Sapa  2 , Karolina Pytka  2
Affiliations

Potential Anti-Amnesic Activity of a Novel Multimodal Derivative of Salicylamide, JJGW08, in Mice

Elżbieta Żmudzka et al. Pharmaceuticals (Basel). .

Abstract

Memory impairments constitute a significant problem worldwide, and the COVID-19 pandemic dramatically increased the prevalence of cognitive deficits. Patients with cognitive deficits, specifically memory disturbances, have underlying comorbid conditions such as schizophrenia, anxiety, or depression. Moreover, the available treatment options have unsatisfactory effectiveness. Therefore, there is a need to search for novel procognitive and anti-amnesic drugs with additional pharmacological activity. One of the important therapeutic targets involved in the modulation of learning and memory processes are serotonin receptors, including 5-HT1A, 5-HT6, and 5-HT7, which also play a role in the pathophysiology of depression. Therefore, this study aimed to assess the anti-amnesic and antidepressant-like potential of JJGW08, a novel arylpiperazine alkyl derivative of salicylamide with strong antagonistic properties at 5-HT1A and D2 receptors and weak at 5-HT2A and 5-HT7 receptors in rodents. First, we investigated the compound's affinity for 5-HT6 receptors using the radioligand assays. Next, we assessed the influence of the compound on long-term emotional and recognition memory. Further, we evaluated whether the compound could protect against MK-801-induced cognitive impairments. Finally, we determined the potential antidepressant-like activity of the tested compound. We found that JJGW08 possessed no affinity for 5-HT6 receptors. Furthermore, JJGW08 protected mice against MK-801-induced recognition and emotional memory deficits but showed no antidepressant-like effects in rodents. Therefore, our preliminary study may suggest that blocking serotonin receptors, especially 5-HT1A and 5-HT7, might be beneficial in treating cognitive impairments, but it requires further investigation.

Keywords: anti-amnesic effect; antidepressant-like activity; cognition; long-term memory; serotonin receptors.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The influence of JJGW08 on the latency in the step-through passive avoidance task in mice. The experiment consisted of two sessions, i.e., the acquisition and the retention trial. In the acquisition trial mice were placed individually in the light chamber of the apparatus, with the door opening after 30 s. When the animal crossed to the dark chamber, the door closed, and the animal was punished with an electric shock (0.8 mA, 2 s). JJGW08 was administered intraperitoneally (ip) 30 min before the start of the experiment. The control group received ip 0.9% NaCl solution. On the second day of the test, mice were placed again in the light chamber, and the latency was measured for a maximum of 300 s (without an electrical impulse). Values are expressed as means ± SD, n = 8 mice per group. Statistical analysis: two-way ANOVA with repeated measures (Bonferroni post hoc).
Figure 2
Figure 2
The influence of JJGW08 on the latency after the MK-801 administration in the step-through passive avoidance task in mice. The experiment consisted of two sessions, i.e., the acquisition and retention trial. In the acquisition trial, mice were placed individually in the light chamber of the apparatus, with the door opening after 30 s. When the animal crossed to the dark chamber, the door closed, and the animal was punished with an electric shock (0.8 mA, 2 s). JJGW08 was administered intraperitoneally (ip) 30 min before the test, while MK-801 (0.125 mg/kg) was administered ip 15 min before the start of the experiment to induce memory impairments. The control group received ip 0.9% NaCl solution in two injections or 0.9% NaCl solution and MK-801 (0.125 mg/kg; ip). On the second day of the test, mice were placed again in the light chamber, and the latency was measured for a maximum of 300 s (without electrical impulse). Values are expressed as means ± SD, n = 8 mice per group. Statistical analysis: two-way ANOVA with repeated measures (Bonferroni post hoc) * p < 0.05, ** p < 0.01, *** p < 0.001.
Figure 3
Figure 3
The influence of JJGW08 on the novel object exploration time in mice. The experiment consisted of two sessions. On the first day, mice were placed and left in cages until they reached a total exploration time of 20 s for both identical objects, but no longer than 10 min. JJGW08 was administered ip 30 min before the start of the experiment. The control group received ip 0.9% NaCl solution. On the second day, mice were placed again in cages, where one object was changed to a new one. The mice remained in the cage until they reached a total exploration time of 20 s for both objects, but no longer than 10 min. Values are expressed as means ± SD, n = 8–10 mice per group. Statistical analysis: one-sample t-test * p < 0.05, ** p < 0.01 vs. chance level = 10 s.
Figure 4
Figure 4
The influence of JJGW08 on the novel object exploration time after the MK-801 administration in mice. The experiment consisted of two sessions. On the first day, mice were placed and left in cages until they reached a total exploration time of 20 s for both identical objects, but no longer than 10 min. The tested compound was administered intraperitoneally (ip) 30 min before, while MK-801 (0.125 mg/kg) was administered ip 15 min before the start of the experiment to induce memory impairments. The control group received 0.9% NaCl solution ip in two injections or 0.9% NaCl solution ip and MK-801 (0.125 mg/kg; ip). On the second day, mice were placed again in cages, where one object was changed to a new one. The mice remained in the cage until they reached a total exploration time of 20 s for both objects, but no longer than 10 min. Values are expressed as means ± SD, n = 8–10 mice per group. Statistical analysis: one-sample t-test ** p < 0.01 vs. chance level = 10.
Figure 5
Figure 5
The effect of JJGW08 on the immobility, climbing, and swimming time in the forced swim test in mice. Mice were placed in water tanks, and the immobility time, as well as swimming and climbing time, were measured for 4 min (after a 2-min adaptation period). JJGW08 was administered intraperitoneally (ip) 30 min before the test. The control group received an injection of 0.9% NaCl (ip). Values are expressed as means ± SD in case of one-way ANOVA (climbing and swimming) or medians with interquartile range in case of Kruskal–Wallis test (immobility), n = 8–10 mice per group. Statistical analysis: one-way ANOVA (Newman–Keuls post hoc) or Kruskal–Wallis (Dunn’s post hoc), * p < 0.05, ** p < 0.01, *** p < 0.001 vs. control group.
Figure 6
Figure 6
The effect of JJGW08 on the immobility time in the tail suspension test in mice. Mice were suspended by the tail (50 cm above the ground) with adhesive tape (1 cm wide), and the immobility time was measured for 6 min. JJGW08 was administered intraperitoneally (ip) 30 min before the test. The control group received an injection of 0.9% NaCl (ip). Values are expressed as medians with interquartile range, n = 10 mice per group. Statistical analysis: Kruskal–Wallis (Dunn’s post hoc), * p < 0.05, ** p < 0.01 vs. control group.
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