scholarly journals α-Conotoxin TxID and [S9K]TxID, α3β4 nAChR Antagonists, Attenuate Expression and Reinstatement of Nicotine-Induced Conditioned Place Preference in Mice

Marine Drugs ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. 646
Author(s):  
Xiaodan Li ◽  
Shen You ◽  
Jian Xiong ◽  
Yamin Qiao ◽  
Jinpeng Yu ◽  
...  

Tobacco smoking has become a prominent health problem faced around the world. The α3β4 nicotinic acetylcholine receptor (nAChR) is strongly associated with nicotine reward and withdrawal symptom. α-Conotoxin TxID, cloned from Conus textile, is a strong α3β4 nAChR antagonist, which has weak inhibition activity of α6/α3β4 nAChR. Meanwhile, its analogue [S9K]TxID only inhibits α3β4 nAChR (IC50 = 6.9 nM), and has no inhibitory activity to other nAChRs. The present experiment investigates the effect of α3β4 nAChR antagonists (TxID and [S9K]TxID) on the expression and reinstatement of nicotine-induced conditioned place preference (CPP) and explores the behaviors of acute nicotine in mice. The animal experimental results showed that TxID and [S9K] TxID could inhibit the expression and reinstatement of CPP, respectively. Moreover, both had no effect in acute nicotine experiment and the locomotor activity in mice. Therefore, these findings reveal that the α3β4 nAChR may be a potential target for anti-nicotine addiction treatment. [S9K]TxID, α3β4 nAChR antagonist, exhibit a superior effect for anti-nicotine addiction, which is promising to develop a novel smoking cessation drug.

Marine Drugs ◽  
2019 ◽  
Vol 17 (9) ◽  
pp. 490 ◽  
Author(s):  
You ◽  
Li ◽  
Xiong ◽  
Zhu ◽  
Zhangsun ◽  
...  

Abstract: α-Conotoxin TxIB is a specific antagonist of α6/α3β2β3(α6β2*) nicotinic acetylcholine receptor (nAChR) with an IC50 of 28 nM. Previous studies have shown that α6β2* nAChRs are abundantly expressed in midbrain dopaminergic neurons and play an important role in mediating the mechanism of nicotine and other drugs reward effect. It provided important targets for the development of anti-addiction drugs. The present study evaluated the pharmacological activity of TxIB in vivo with conditioned place preference (CPP) model, which were induced by subcutaneous injection (s.c.) of nicotine (NIC, 0.5 mg/kg). α-Conotoxin TxIB inhibited the expression and reinstatement of CPP in mice dose-dependently, but had no significant effect on locomotor activity. The concentrations of dopamine (DA), γ-aminobutyric acid (GABA) and noradrenaline (NE) in different brain regions were measured by enzyme-linked immunosorbent assay (ELISA). We found that TxIB could inhibit the concentrations of DA, GABA and NE in different brain regions (such as nucleus accumbens (NAc), hippocampus (HIP) and prefrontal cortex (PFC)) in NIC-induced mice. The concentrations of DA and NE were decreased in ventral tegmental area (VTA), while GABA had little change. The current work described the inhibition activity of TxIB in NIC-induced CPP, suggesting that α6β2* nAChR-targeted compound may be a promising drug for nicotine addiction treatment.


Drug Research ◽  
2020 ◽  
Vol 70 (09) ◽  
pp. 410-416
Author(s):  
Leila Etemad ◽  
Hadi Farkhari ◽  
Mohaddeseh Sadat Alavi ◽  
Ali Roohbakhsh

Abstract Objective Dihydromyricetin (DHM), a natural flavonoid, is used to reduce alcohol hangover. It has a modulatory role on GABAA receptors with significant effects on seizure and anxiety in animal models. We aimed to evaluate the effect of DHM on morphine conditioned place preference (CPP) and withdrawal sings following morphine dependence using animal models. Methods The effect of DHM (1, 2 and 5 mg/kg, intraperitoneal; ip) on the acquisition and expression of morphine-induced CPP was evaluated in male mice. Administration of morphine for three consecutive days induced physical dependence. The withdrawal signs such as jumping and defecation were precipitated by administration of naloxone (8 mg/kg, ip). The effect of DHM on the development of physical dependence was assessed by injection of DHM before morphine administrations. Results DHM, at the dose of 5 mg/kg, reduced expression of morphine CPP with an increase in the locomotor activity. DHM, at the doses of 2 and 5 mg/kg, also reduced development of morphine CPP. DHM alleviated development of morphine-induced physical dependence at the dose of 1, 2, and 5 mg/kg by decreasing jumping and defecation. Conclusion These results indicated that DHM decreased acquisition and expression of morphine CPP and inhibited development of morphine-induced physical dependence.


2014 ◽  
Vol 83 ◽  
pp. 128-136 ◽  
Author(s):  
Ewa Taracha ◽  
Ewelina Kaniuga ◽  
Stanisław J. Chrapusta ◽  
Piotr Maciejak ◽  
Lech Śliwa ◽  
...  

1992 ◽  
Vol 106 (3) ◽  
pp. 330-336 ◽  
Author(s):  
S. E. Hemby ◽  
G. H. Jones ◽  
J. B. Justice ◽  
D. B. Neill

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