High doses of testosterone increase anticonflict behaviour in rat
Introduction
The underlying principle for many of the so-called animal models of anxiety is that a rat is put in a conflict situation in which the urge to display a reward-generating behaviour (such as licking a tube, or pressing a lever for food) is suppressed by the fear of punishment (usually an electroshock). The assumption that this paradigm may reflect human anxiety is based mainly on the fact that many anxiolytic drugs increase punished responding (Vogel et al., 1971, Griebel, 1995).
According to another hypothesis, enhanced punished responding in animal models of anxiety may reflect reduced waiting ability, or reduced impulse control, rather than anxiolysis (Soubrié, 1986, Eriksson and Humble, 1990). The observation that serotonin synthesis inhibition exerts a forceful anticonflict effect (Griebel, 1995) may be taken as support for this concept; thus, both clinical studies and animal experiments suggest that a reduction in serotonergic transmission is associated with lowered impulse control. In contrast, the assumption that inhibition of serotonin synthesis should lead to anxiolysis is not supported by clinical findings (see Eriksson and Humble, 1990).
High doses of testosterone have been reported to reduce impulse control in man (Su et al., 1993, Lukas, 1996, Bahrke et al., 1996); in contrast, no anxiolytic effects of this treatment have been reported. If the Vogel conflict test does reflect impulsivity, high doses of testosterone would be expected to increase punished responding; on the other hand, if the Vogel conflict test is sensitive to anxiolytic drugs only, testosterone would be inactive (or would exert proconflict effects).
Section snippets
Animals
Male Wistar rats (Bee Kay, Sollentuna, Sweden; 200–225 g) were kept in group cages (five in each) under controlled light-dark conditions (light on at 05:00 h and off at 19:00 h) with constant temperature (21°C) and humidity (65%). Until the start of the experiments, free access to food and water was allowed.
Experiment 1
Semipermeable silicone tubings (length: 50 mm, five tubings/rat) filled with crystalline testosterone (4-androsten-17-β-ol-3-one, Sigma, 40 mg/tubing) were implanted subcutaneously in the
Experiment 1
Body weight of rats treated with high doses of testosterone for 8 weeks was significantly lower (330±6 g) than that of controls (385±10 g) (n=8 in each group, P<0.001).
In the Vogel conflict experiment, testosterone treated rats (n=8) accepted 57±6 shocks during the 10-min testing period; controls (n=8) accepted 26±7 shocks (P<0.004). The two groups did not differ significantly with respect to non-punished drinking (testosterone: 26±5, controls: 16±3; P=0.1). Also, they did not differ with
Discussion
Many reports suggest that high doses of testosterone may reduce impulse control and promote aggression in man (Su et al., 1993, Lukas, 1996, Bahrke et al., 1996). In contrast, testosterone has not been attributed anxiolytic effects; rather, anxiety is one of the unwanted effects reported by abusers of anabolic steroids (Perry et al., 1990). Thus, the present observation that testosterone increases punished responding in rat supports the theory put forward by Soubrié (1986) that the anticonflict
Acknowledgements
This study was supported by the Knut and Alice Wallenberg's Foundation, the Swedish Medical Research Council (grant no. 8668), The Foundation of the Söderström-Königska Nursing Home, and Fredrik Thuring's Foundation. Excellent technical assistance was provided by Ms Inger Oscarsson and Ms Gunilla Bourghardt.
References (14)
Testosterone and persistence in mice
Anim. Behav.
(1977)- et al.
Treatment with an anabolic-androgenic steroid affects anxiety-related behavior and alters the sensitivity of cortical GABAA receptors in the rat
Horm. Behav.
(1993) - et al.
The relationship between circulating testosterone levels and male sexual behavior in rats
Horm. Behav.
(1977) 5-Hydroxytryptamine-interacting drugs in animal models of anxiety disorders: more than 30 years of research
Pharm. Ther.
(1995)- et al.
Psychological and behavioural effects of endogenous testosterone and anabolic-androgenic steroids. An update
Sports Med.
(1996) - Eriksson, E., Humble, M., 1990. Serotonin in psychiatric pathophysiology. In: Pohl, R., Gershon, S. (Eds.), The...
CNS effects and abuse liability of anabolic-androgenic steroids
Annu. Rev. Pharm. Toxicol.
(1996)
Cited by (66)
Oxandrolone treatment in juvenile rats induced anxiety-like behavior in young adult animals
2021, Neuroscience LettersSerotonin type-3 receptors differentially modulate anxiety and aggression during withdrawal from adolescent anabolic steroid exposure
2020, Hormones and BehaviorCitation Excerpt :However, like early preclinical studies of AAS effects on aggression (Bronson, 1996; Martinez-Sanchis et al., 1998), the effects of AAS on anxiety are inconsistent. For instance, in rats and mice, AAS reduce (Aikey et al., 2002; Bing et al., 1998; Bitran et al., 1993; Fernandez-Guasti and Martinez-Mota, 2005; Ovsiukova et al., 2003), enhance (Agis-Balboa et al., 2009; Ambar and Chiavegatto, 2009; Costine et al., 2010; Minkin et al., 1993; Parrilla-Carrero et al., 2009; Rocha et al., 2007; Rojas-Ortiz et al., 2006), or they have no effect (Barreto-Estrada et al., 2004) on anxious behavior. One limitation of these studies is that they provide no information of the effect(s) of AAS on the relationship between aggressive and anxious behaviors.
Effects of gonadectomy and serotonin depletion on inter-individual differences in anxiety-like behaviour in male Wistar rats
2016, Behavioural Brain Research