High doses of testosterone increase anticonflict behaviour in rat

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Abstract

Male rats exposed to high levels of testosterone for 8 weeks, or to one high dose of testosterone 24 h before testing, displayed an increase in punished responding in the Vogel conflict test. The findings may be taken as indirect support for the assumption that the conflict paradigm reflects not only anxiety but also impulsivity.

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.

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