HBK-15- a multimodal compound- induces procognitive effects through modulating hippocampal LTP and enhancing theta-gamma coupling in mice

Authors
Lustyk K, Sałaciak K, Jakubczyk M, Jastrzębska-Więsek M, Partyka A, Wesołowska A, Marona H, Pytka K

Lab
Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland

Journal
Neurochem Res

Abstract
Anxiety is a common mental disorder, and its prevalence has lately increased because of the COVID-19 pandemic. Unfortunately, the available anxiolytics are often ineffective, and most possess addictive potential. Thus, searching for novel compounds is essential. In our previous studies, we selected a multimodal compound, HBK-15, which showed a fast antidepressant-like effect in animal models of depression. HBK-15 demonstrated a high affinity for serotonin 5-HT1A receptors and moderate for 5-HT7, dopamine D2, and α1-adrenoceptors. Based on the receptor profile and preliminary studies, we aimed to investigate the anxiolytic potential of HBK-15 using the conditioned-response rat model of anxiety, i.e., the Vogel drinking test. We performed hot plate and free-drinking tests to exclude false positive results in the Vogel test. Using radioligand binding studies, we also investigated the affinity of the compound for the selected biological targets, which play a role in anxiety. Our experiments revealed that HBK-15 showed an anxiolytic-like effect in rats (5 mg/kg) without influencing the pain threshold or the amount of water consumed in the free-drinking test. Furthermore, the tested compound did not show a significant affinity for the selected biological targets, which suggests that its anxiolytic-like mechanism of action could be connected with the interaction with other receptors. This study indicates that multimodal compounds with a receptor profile similar to HBK-15 could be an attractive therapeutic option for patients with a generalized anxiety disorder. However, more studies are required to determine the exact mechanism of action of HBK-15 and its safety profile.

BIOSEB Instruments Used:
Cold Hot Plate Test (BIO-CHP)