title: Anabolic-androgenic steroids impair set-shifting and reversal learning in male rats.
abstract: Anabolic-androgenic steroid (AAS) abuse is prevalent not only among elite athletes, but is increasingly common in high school and collegiate sports. AAS are implicated in maladaptive behaviors such as increased aggression and risk taking, which may result from impaired cognition. Because they affect dopamine function in prefrontal cortical (PFC)-striatal circuitry, AAS may disrupt PFC-dependent processes such as behavioral flexibility. This was the focus of the present study. Adolescent male Long-Evans rats were treated chronically with high-dose testosterone (7.5mg/kg in water with 13% cyclodextrin) or vehicle sc, and tested for set-shifting and reversal-learning. For set-shifting, rats were trained on a visual cue task (VCT), then were shifted to a direction cue task (DCT), or vice-versa. For reversal learning, rats were first trained on VCT and were then required to press the opposite lever. 2-cue set-shifting introduced a novel paradigm in which rats shifted from a 1-Light Visual Task (1LVT) to a tone cue task (TCT). Testosterone-treated rats were significantly impaired on the set-shift from DCT to VCT compared to vehicle-treated controls (trials to criterion: vehicle 240.9±29.9, testosterone 388.3±59.3, p<0.05). However, on the set-shift from VCT to DCT, testosterone did not affect performance. During reversal-learning, testosterone significantly increased trials to criterion (vehicle: 495.9±91.8 trials, testosterone: 793.7±96.7 trials, p<0.05). In 2-cue set-shifting, testosterone diminished performance and the difference showed borderline significance (vehicle: 443.2±84.4 trials, testosterone: 800.4±178.2 trials, p=0.09). Our results show that testosterone impairs behavioral flexibility and have implications for understanding cognitive and behavioral changes in human AAS users.
authors: Neuroscience Graduate Program, University of Southern California, Los Angeles, CA 90033, USA.
authors: Kathryn G
authors: KG
authors: Wallin
authors: Department of Cell and Neurobiology, Keck School of Medicine of the University of Southern California, 1333 San Pablo St., BMT 408, Los Angeles, CA 90033, USA. Electronic address: riw@usc.edu.
authors: Ruth I
authors: RI
authors: Wood
mesh_terms: D045930:Anabolic Agents / Q000494:pharmacology*; D000818:Animals; D001288:Attention / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects*; D003463:Cues; D008297:Male; D010775:Photic Stimulation; D051381:Rats; D020318:Rats, Long-Evans; D012193:Reversal Learning / Q000187:drug effects*; D012718:Set, Psychology; D013739:Testosterone / Q000494:pharmacology*
chemical_list: D045930:Anabolic Agents; D013739:Testosterone
keywords: Anabolic agents; Cognition; Food reward; Operant behavior; Testosterone
references: Nature. 1972 Jun 9;237(5354):343-6
references: 4557402
references: Behav Brain Res. 2008 Jun 26;190(1):85-96
references: 18359099
references: Drug Alcohol Depend. 2013 Jun 1;130(1-3):208-14
references: 23253252
references: Front Neurosci. 2013 Apr 19;7:62
references: 23626521
references: Eur J Neurosci. 2001 Jan;13(2):291-6
references: 11168533
references: Cereb Cortex. 2007 Jun;17(6):1444-53
references: 16920882
references: Neurobiol Learn Mem. 2007 Jul;88(1):75-81
references: 17467309
references: J Child Psychol Psychiatry. 2006 Mar-Apr;47(3-4):296-312
references: 16492261
references: Horm Behav. 2008 May;53(5):647-58
references: 18343381
references: Behav Neurosci. 1996 Dec;110(6):1478-86
references: 8986348
references: J Gen Psychol. 1948 Jul;39:15-22
references: 18889466
references: Neurosci Lett. 2007 Jan 29;412(2):168-72
references: 17123707
references: J Comp Neurol. 2000 Nov 27;427(4):617-33
references: 11056468
references: J Neurosci. 2011 Mar 16;31(11):4290-7
references: 21411670
references: Neuropsychopharmacology. 2006 Feb;31(2):297-309
references: 16012531
references: J Cogn Neurosci. 2010 Oct;22(10):2357-68
references: 19925198
references: Physiol Behav. 1998 Jan;63(2):287-95
references: 9423971
references: Psychopharmacology (Berl). 2010 Apr;209(3):271-81
references: 20186395
references: Horm Behav. 2006 Apr;49(4):519-26
references: 16388806
references: Neuropsychopharmacology. 2009 Jul;34(8):2041-52
references: 19262467
references: Endocr Rev. 2014 Jun;35(3):341-75
references: 24423981
references: Child Dev. 1964 Dec;35:1343-59
references: 14251379
references: Neurobiol Learn Mem. 2008 May;89(4):567-73
references: 18054257
references: Psychopharmacology (Berl). 2006 Nov;188(4):567-85
references: 16670842
references: Nat Rev Neurosci. 2007 Nov;8(11):844-58
references: 17948030
references: J Neurosci. 2000 Jun 1;20(11):4320-4
references: 10818167
references: J Neurosci. 2006 Aug 23;26(34):8810-8
references: 16928870
references: Dev Psychobiol. 1983 Mar;16(2):83-109
references: 6339302
references: J Neurosci. 2004 Jan 21;24(3):702-10
references: 14736856
references: Psychoneuroendocrinology. 2014 Feb;40:201-12
references: 24485492
references: Behav Brain Res. 2003 Nov 30;146(1-2):97-103
references: 14643463
references: Horm Behav. 2007 Feb;51(2):183-94
references: 16942768
references: Physiol Behav. 2013 Feb 17;110-111:6-12
references: 23266798