Anti-aggressive effects of agonists at 5-HT1B receptors in the dorsal raphe nucleus of mice.
BACKGROUND
In rodents, serotonin 1B (5-HT(1B)) agonists specifically reduce aggressive behaviors, including several forms of escalated aggression. One form of escalated aggression is seen in mice that seek the opportunity to attack another mouse by accelerating their responding during a fixed interval (FI) schedule. Responses preceding the opportunity to attack may reflect aggressive motivation.


OBJECTIVE
This study investigated the effects of two 5-HT(1B) receptor agonists on the motivation to fight and the performance of heightened aggression.


METHODS
Male mice were housed as "residents" and performed nose-poke responses on an FI 10-min schedule with the opportunity to briefly attack an "intruder" serving as the reinforcer. In the first experiment, the 5-HT(1B) receptor agonist, CP-94,253 (0-10 mg/kg, IP), was given 30 min before the FI 10 schedule. To confirm that CP-94,253 achieved its effects via 5-HT(1B) receptors, the 5HT(1B/1D) receptor antagonist, GR 127,935 (10 mg/kg, IP) was administrated before the agonist injection. In the second experiment, the 5-HT(1B) agonist CP-93,129 (0-1.0 microg) was microinjected into the dorsal raphe 10 min before the FI 10 schedule.


RESULTS
The agonists had similar effects on all behaviors. CP-94,253 and CP-93,129 significantly reduced the escalated aggression towards the intruder at doses lower than those required to affect operant responding. The highest doses of CP-94,253 (10 mg/kg) and CP-93,129 (1.0 microg) decreased the rate and accelerating pattern of responding during the FI 10 schedule; lower doses were less effective. GR 127,935 antagonized CP-94,253's effects on all other behaviors, except response rate.


CONCLUSIONS
These data extend the anti-aggressive effects of 5-HT(1B) agonists to a type of escalated aggression that is rewarding and further suggest that these effects are associated with actions at 5-HT(1B) receptors in the dorsal raphe.
Bannai
Makoto
M
Department of Psychology, Tufts University, Medford and Boston, MA, USA.
Fish
Eric W
EW
Faccidomo
Sara
S
Miczek
Klaus A
KA
D000374:Aggression / Q000187:drug effects*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003216:Conditioning, Operant; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D010069:Oxadiazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000187:drug effects* / Q000378:metabolism; D058825:Serotonin 5-HT1 Receptor Agonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
C097067:CP 94253; D010069:Oxadiazoles; D010879:Piperazines; D011725:Pyridines; D011758:Pyrroles; D058825:Serotonin 5-HT1 Receptor Agonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C065046:3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo(3,2-b)pyrid-5-one; C090701:GR 127935