The Social and Nonsocial Impact of Anabolic Androgenic Steroids and Low Serotonin in Pubertal Male Rats: A Behavioral and Neurochemical Analysis

Abstract

This study' s purpose was to determine the behavioral and neurochemical impact of low serotonin (5-HT), via p-chlorophenylalanine (PCPA) injections, in males exposed to anabolic androgenic steroids (AAS) during puberty. Social and non-social behavioral tests were conducted and 5-HT-related neurochemical measurements were taken. Behavioral and neurochemical measures were also assessed following discontinuation of PCP A in combination with the AAS testosterone propionate (TP) to determine the permanence of these effects. Beginning at 26 days of age, 30 gonadally intact male pubescent rats received injections of PCPA (50 mg/kg) or saline three times a week for 9 weeks. Starting at puberty (Day 40), animals received injections ofTP (5 mg/kg) five days a week for 7 weeks. Five groups were studied: TP, PCPA, TP + PCPA, Control and Withdrawal. Behavioral tests began at 61 days of age. The withdrawal group received a second set of behavioral tests 10 days after their last injection of TP + PCP A. At the end of behavioral testing the brainstem, striatum, hypothalamus, hippocampus and cortex were removed and levels of 5-HT, 5-hydroxyindoleaceticacid (5-HIAA), and tryptophan (TRP) were determined using high performance liquid chromatography (HPLC). Results indicated that locomotor activity was reduced by PCP A, whether alone or in combination with TP. PCP A alone also elicited a longer latency to nose poke in a separate non-social and novel environment. No significant differences were found between any of the sexual behavior measures. The first aggression tests were conducted with and without provocation, which was induced using a mild tail pinch. Without provocation the PCP A group displayed significantly more dominance mounts than controls. With provocation, PCP A and TP+PCP A treated males exhibited the highest levels of aggression compared to controls. In the social aggression test, animals receiving TP alone and TP + PCP A exhibited heightened aggression compared to controls. Following withdrawal, there were no significant differences in any behavioral measure. HPLC revealed that 5-HT levels were depleted approximately 80% in each region examined for the TP+PCPA and PCP A alone groups. In the withdrawal group, levels of 5-HT were similar to those observed in controls. TP was found to significantly increase 5-HT levels in the frontal cortex and also decreased 5-HIAA levels in the hypothalamus. Taken together these data suggest that AAS exposure during adolescence increases the likelihood of an animal to react to provocation or a threatening environment aggressively. When AAS exposure during adolescence is combined with low 5-HT animals also tend to exhibit behaviors found in animals receiving just PCP A, such as reacting aggressively toward non-threatening animals and exhibiting decreases in locomotor activity. It also provides evidence that the observed behavioral and neurochemical effects may be reversible.