'Roid rage in rats? Testosterone effects on aggressive motivation, impulsivity and tyrosine hydroxylase

Abstract

In humans and animals, anabolic-androgenic steroids (AAS) increase aggression, but the underlying behavioral mechanisms are unclear. AAS may increase the motivation to fight. Alternatively, AAS may increase impulsive behavior, consistent with the popular image of 'roid rage. To test this, adolescent male rats were treated chronically with testosterone (7.5mg/kg) or vehicle and tested for aggressive motivation and impulsivity. Rats were trained to respond on a nose-poke on a 10 min fixed-interval schedule for the opportunity to fight in their home cage with an unfamiliar rat. Although testosterone increased aggression (6.3±1.3 fights/5 min vs 2.4±0.8 for controls, p<0.05), there was no difference in operant responding (28.4±1.6 nose-pokes/10 min for testosterone, 32.4±7.0 for vehicle). This suggests that testosterone does not enhance motivation for aggression. To test for impulsivity, rats were trained to respond for food in a delay-discounting procedure. In an operant chamber, one lever delivered one food pellet immediately, the other lever gave 4 pellets after a delay (0, 15, 30 or 45 s). In testosterone- and vehicle-treated rats, body weights and food intake did not differ. However, testosterone-treated rats chose the larger, delayed reward more often (4.5±0.7 times in 10 trials with 45 s delay) than vehicle controls (2.5±0.5 times, p<0.05), consistent with a reduction in impulsive choice. Thus, although chronic high-dose testosterone enhances aggression, this does not include an increase in impulsive behavior or motivation to fight. This is further supported by measurement of tyrosine hydroxylase (TH) by Western immunoblot analysis in brain regions important for motivation (nucleus accumbens, Acb) and executive function (medial prefrontal cortex, PFC). There were no differences in TH between testosterone- and vehicle-treated rats in Acb or PFC. However, testosterone significantly reduced TH (to 76.9±3.1% of controls, p<0.05) in the caudate-putamen, a brain area important for behavioral inhibition, motor control and habit learning.

Fig. 1

Top: Operant responses (mean±SEM) under a fixed-interval (FI) schedule for access to an unfamiliar intruder in a resident–intruder test of aggression in Long–Evans male rats treated chronically with testosterone (closed symbols) or vehicle (open symbols). Operant behavior during initial training (A), and at the end of the study (B). Middle: Aggressive behavior towards the intruder, measured as the number of attacks (C) and latency to the first attack (D). Bottom: Contact with the intruder, measured as total contact (E) and duration of individual contact bouts (F). Asterisks indicate significant differences between treatment groups.

Fig. 2

Physiologic and behavioral measures during a test of delay-discounting for food to assess impulsive behavior. Compared with vehicle-treated rats (open bars), there was no effect of testosterone (closed bars) on body weight (A), food received during the delay-discounting test (B), 24-hour food intake (C), or the percent of unreinforced trials (D).

Fig. 3

Preference for a large food reward across an increasing time delay under a delay-discounting test in Long–Evans male rats. Compared with vehicle-treatment (open circles) testosterone treatment (closed circles) increased preference for the larger reward at longer delay intervals. Asterisks indicate significant differences between treatment groups.

Fig. 4

Top: Western blot assays of tyrosine hydroxylase (TH) and beta-tubulin in caudate-putamen from representative Long–Evans male rats (n=2 each) treated chronically with vehicle (left) or testosterone (right). Bottom: Levels of TH in microdissected brain regions from testosterone-(closed bars) or vehicle-treated rats (open bars). ACB: nucleus accumbens, CPu: caudate-putamen, PFC: medial prefrontal cortex, VTA/SN: ventral tegmental area/substantia nigra. Asterisks indicate significant differences between treatment groups.