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Anabolic-androgenic steroids (AAS) increase sensitivity to uncertainty by inhibition of dopamine D1 and D2 receptors
Univ Southern Calif, Neurosci Grad Program, Los Angeles, CA 90033 USA.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Univ Southern Calif, Keck Sch Med, Dept Integrated Anat Sci, 1333 San Pablo St,BMT 401, Los Angeles, CA 90033 USA.
Univ Southern Calif, Keck Sch Med, Dept Integrated Anat Sci, 1333 San Pablo St,BMT 401, Los Angeles, CA 90033 USA.
2018 (English)In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 235, no 4, p. 959-969Article in journal (Refereed) Published
Abstract [en]

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

Place, publisher, year, edition, pages
SPRINGER , 2018. Vol. 235, no 4, p. 959-969
Keywords [en]
Anabolic agents, Dopamine, Decision making, Operant behavior, Food reward
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:uu:diva-353121DOI: 10.1007/s00213-017-4810-7ISI: 000428421300004PubMedID: 29242988OAI: oai:DiVA.org:uu-353121DiVA, id: diva2:1216031
Available from: 2018-06-11 Created: 2018-06-11 Last updated: 2018-06-11Bibliographically approved

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