The effect of buspirone on normal and hypoarousal-driven abnormal aggression in rats.
Aggressiveness is associated with decreased glucocorticoid production, autonomic hypoarousal, and social deficits in antisocial personality disorder and its childhood antecedent conduct disorder. We showed previously that experimentally induced chronic glucocorticoid deficiency leads to abnormal forms of attack, autonomic hypoarousal, and social deficits in rats. We also showed that serotonergic neurotransmission, which downregulates aggressiveness in normal rats appears to lose its aggression-controlling role in glucocorticoid-deficient rats. We suggested that abnormal aggression develops in such rats as a consequence of serotonergic disturbances that result from chronic glucocorticoid deficiency. Here we assessed the effects of the serotonergic anxiolytic buspirone on aggressive behavior in normal and glucocorticoid-deficient rats. Noteworthy, this compound is frequently used in the clinic to control moderate aggression problems. As expected, buspirone dose-dependently reduced the duration of agonistic behaviors in normal rats exposed to resident/intruder conflicts. Similar to earlier experiments, glucocorticoid deficiency dramatically increased the share of attacks directed towards vulnerable body parts of the opponents (head, throat and belly). Surprisingly, 1 and 5 mg/kg buspirone dramatically increased the frequency of biting attacks in glucocorticoid-deficient rats. The share of vulnerable attacks remained as high as in vehicle-treated glucocorticoid-deficient rats. These data show that chronic glucocorticoid deficiency disturbs serotonergic neurotransmission, which reverses the aggression-related effects of the serotonergic agent buspirone. This finding is in line with disparate human findings on the effects of serotonergic agents on aggression in antisocial personality disordered people.
Haller
Jozsef
J
Institute of Experimental Medicine, Budapest, Hungary. haller@koki.hu
Horváth
Zsuzsanna
Z
Bakos
Nikoletta
N
D000315:Adrenalectomy; D000374:Aggression / Q000187:drug effects*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001143:Arousal / Q000502:physiology*; D002065:Buspirone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D005938:Glucocorticoids / Q000172:deficiency; D051381:Rats; D017208:Rats, Wistar; D012919:Social Behavior
D014151:Anti-Anxiety Agents; D005938:Glucocorticoids; D002065:Buspirone