RATIONALE: Systemic injections of 5-HT(1B) receptor agonists have been shown to have specific anti-aggressive effects in aggressive individuals. One site of action for these drugs is the 5-HT(1B) receptors in the ventral orbitofrontal cortex (VO PFC), an area that has been implicated in the inhibitory control of behavior and is a terminal region for 5-HT projections. OBJECTIVE: To assess the anti-aggressive effects of the 5-HT(1B) receptor agonist CP-94,253 when microinjected into the VO PFC (0.1, 0.56, and 1.0 microg/0.2 microl) or into the infralimbic prefrontal cortex (IL PFC; 1.0 microg/0.2 microl) in separate groups of aggressive resident male mice. To confirm the 5-HT(1B) receptor as the critical site of action for the anti-aggressive effects, the 5-HT(1B/D) antagonist GR-127,935 was microinjected at 10.0 microg/0.2 microl into the VO PFC. After recovery from surgery, the anti-aggressive effects of microinjected CP-94,253 were studied during 5-min resident-intruder confrontations that were recorded and analyzed. RESULTS: Microinjections of CP-94,253 (0.56 and 1.0 microg/0.2 microl) dose-dependently reduced the frequency of attack bites and sideways threats. This effect was behaviorally specific because non-aggressive motor activities were not significantly altered by the drug. In the IL vmPFC or in an area lateral to the VO PFC, CP-94,253 (1.0 microg/0.2 microl) did not have significant behavioral effects. CONCLUSIONS: The results highlight the 5-HT(1B) receptors in the VO PFC as a particularly important site for the inhibition of species-typical aggressive behavior in male mice.
RATIONALE: Systemic injections of 5-HT(1B) receptor agonists have been shown to have specific anti-aggressive effects in aggressive individuals. One site of action for these drugs is the 5-HT(1B) receptors in the ventral orbitofrontal cortex (VO PFC), an area that has been implicated in the inhibitory control of behavior and is a terminal region for 5-HT projections. OBJECTIVE: To assess the anti-aggressive effects of the 5-HT(1B) receptor agonist CP-94,253 when microinjected into the VO PFC (0.1, 0.56, and 1.0 microg/0.2 microl) or into the infralimbic prefrontal cortex (IL PFC; 1.0 microg/0.2 microl) in separate groups of aggressive resident male mice. To confirm the 5-HT(1B) receptor as the critical site of action for the anti-aggressive effects, the 5-HT(1B/D) antagonist GR-127,935 was microinjected at 10.0 microg/0.2 microl into the VO PFC. After recovery from surgery, the anti-aggressive effects of microinjected CP-94,253 were studied during 5-min resident-intruder confrontations that were recorded and analyzed. RESULTS: Microinjections of CP-94,253 (0.56 and 1.0 microg/0.2 microl) dose-dependently reduced the frequency of attack bites and sideways threats. This effect was behaviorally specific because non-aggressive motor activities were not significantly altered by the drug. In the IL vmPFC or in an area lateral to the VO PFC, CP-94,253 (1.0 microg/0.2 microl) did not have significant behavioral effects. CONCLUSIONS: The results highlight the 5-HT(1B) receptors in the VO PFC as a particularly important site for the inhibition of species-typical aggressive behavior in male mice.
Authors: L Matzen; C van Amsterdam; W Rautenberg; H E Greiner; J Harting; C A Seyfried; H Böttcher Journal: J Med Chem Date: 2000-03-23 Impact factor: 7.446
Authors: Klaus A Miczek; Rosa M M de Almeida; Edward A Kravitz; Emilie F Rissman; Sietse F de Boer; Adrian Raine Journal: J Neurosci Date: 2007-10-31 Impact factor: 6.167
Authors: Dirson João Stein; Klaus A Miczek; Aldo Bolten Lucion; Rosa Maria Martins de Almeida Journal: Psychopharmacology (Berl) Date: 2013-07-05 Impact factor: 4.530
Authors: David Matuskey; Zubin Bhagwagar; Beata Planeta; Brian Pittman; Jean-Dominique Gallezot; Jason Chen; Jane Wanyiri; Soheila Najafzadeh; Jim Ropchan; Paul Geha; Yiyun Huang; Marc N Potenza; Alexander Neumeister; Richard E Carson; Robert T Malison Journal: Biol Psychiatry Date: 2013-11-28 Impact factor: 13.382
Authors: Klaus A Miczek; Joseph F DeBold; Lara S Hwa; Emily L Newman; Rosa M M de Almeida Journal: Ann N Y Acad Sci Date: 2015-08-18 Impact factor: 5.691