Anabolic-androgenic steroids (AAS) increase sensitivity to uncertainty by inhibition of dopamine D1 and D2 receptors

合成代谢雄激素类固醇 (AAS) 通过抑制多巴胺 D1 和 D2 受体来增加对不确定性的敏感性

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作者:Kathryn G Wallin-Miller, Frida Kreutz, Grace Li, Ruth I Wood

Background

Anabolic-androgenic steroid abuse is implicated in maladaptive behaviors such as impaired cognition in humans. In a rat model, our lab has shown that testosterone decreases preference for a large/uncertain reward in probability discounting. Other studies have shown that androgens decrease dopamine D1 and D2 receptors in the nucleus accumbens shell, a region important for decision-making behavior in probability discounting. Thus, we attempted to restore selection of the large/uncertain reward in testosterone-treated rats by administering the D2 receptor agonist quinpirole or the D1 receptor agonist SKF81297 and testing probability discounting.

Conclusions

It appears that altered probability discounting behavior in testosterone-treated rats is due to both decreased D1 and D2 receptor function.

Methods

Adolescent male Long-Evans rats were treated chronically with high-dose testosterone (7.5 mg/kg) or vehicle (13% cyclodextrin in water), and tested for probability discounting after injections of saline, 0.1 and 0.5 mg/kg of quinpirole or SKF81297. Rats chose between a small/certain reward (1 sugar pellet, 100% probability) and a large/uncertain reward (4 pellets, decreasing probability: 100, 75, 50, 25, 0%).

Results

Testosterone-treated rats selected the large/uncertain reward significantly less than vehicle-treated controls after saline injection. However, acute injection with 0.1 mg/kg quinpirole increased large/uncertain reward preference in testosterone-treated rats only, indicated by a testosterone × quinpirole interaction. At 0.5 mg/kg, quinpirole increased large/uncertain reward preference in all rats. Acute injection with SKF81297 at 0.1 or 0.5 mg/kg rescued large/uncertain reward preference in testosterone-treated rats by eliminating the difference between groups. Conclusions: It appears that altered probability discounting behavior in testosterone-treated rats is due to both decreased D1 and D2 receptor function.

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