Androgens and estrogens modulate 5-HT1A and 5-HT1B agonist effects on aggression

Intermale offensive aggressive behavior is facilitated by gonadal steroids and inhibited by serotonin (5-MT), presumably through its effects at 5-HT1A and 5-HT1B receptor sites. To examine the interaction between these neuroe ndocrine and neurochemical regulatory systems, CF-1 male mice were gonadect omized and implanted with silastic capsules containing either diethylstilbe strol (DES, a synthetic estrogen), the nonaromatizable androgens methyltrie nolone (R1881) or dihydrotestosterone (DHT), or testosterone (T). Two weeks later, they were given 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, a 5-HT1A agonist; 0.1 or 1.0 mg/kg), CGS12066B (a 5-MT1B agonist; 4.0 or 8. 0 mg/kg), 0.1 or 1.0 mg/kg 8-OH-DPAT + 4.0 mg/kg CGS12066B, or vehicle, and tested for aggression. In the presence of DES, the higher 8-OH-DPAT dose g iven in combination with CGS attenuated aggression in comparison to vehicle controls. When given nonaromatizable androgen (R1881 or DHT), all drug tre atments except 0.1 mg/kg 8-OH-DPAT significantly reduced offensive attack b ehavior. In the presence of T, which provides estrogenic and androgenic sti mulation, aggression scores were significantly reduced when males were give n the high dose of 8-OH-DPAT or CGS12066B, as well as in the 1.0 mg/kg 8-OH -DPAT + CGS12066B condition. Assessments of changes in motor behavior showe d significant impairment when 8.0 mg/kg CGS12066B was administered across a ll hormonal conditions, indicating that reductions in offensive aggression in these treatment groups were nonspecific. The results demonstrate differe ntial effects of the steroidal environment on the ability of 5-HT1A and 5-H T1B agonists to modulate aggression, with estrogens producing a more restri ctive environment than androgens for serotonergic inhibition of male-typica l aggressive behavior. (C) 1999 Elsevier Science Inc.