TY  - JOUR
PY  - 2015//
TI  - Anti-aggressive effects of the selective high-efficacy 'biased' 5-HT1A receptor agonists F15599 and F13714 in male WTG rats
JO  - Psychopharmacology
A1  - de Boer, Sietse F.
A1  - Newman-Tancredi, Adrian
SP  - 937
EP  - 947
VL  - 233
IS  - 6
N2  - BACKGROUND: The serotonin (5-HT) deficiency hypothesis of aggression is being seriously challenged by pharmacological data showing robust anti-aggressive effects of 5-HT1A receptor agonists in dose ranges that concomitantly inhibit 5-HT neurotransmission. Hence, an adequate interpretation of the role of 5-HT activity in regulating aggression depends on elucidating the predominant site of action, i.e., raphe presynaptic autoreceptors versus forebrain postsynaptic heteroreceptors, of these 5-HT1A receptor agonists. <br><br>OBJECTIVES: The present experiments investigated the anti-aggressive properties of the selective 5-HT1A receptor agonists F15599 that preferentially target postsynaptic 5-HT1A heteroreceptors in the frontal cortex and F13714 that more preferentially activates raphe somatodendritic 5-HT1A autoreceptors. <br><br>METHODS: Both 'biased' agonists were acutely administered intraperitoneally in aggressive resident male WTG rats confronting an intruder. <br><br>RESULTS: Systemic administration of F15599 and F13714 exerted very potent (ID50 = 0.095 and 0.0059 mg/kg, respectively) anti-aggressive effects. At 4.5-fold higher dose ranges, the anti-aggressive effects were accompanied by concomitant motor inactivity and/or reduction of social engagement. Pretreatment with WAY-100635 counteracted the behavioural effects of both agonists. <br><br>CONCLUSIONS: Overall, the qualitatively similar but quantitatively different anti-aggressive profiles of F15599 and F13714 largely correspond to their distinct 5-HT1A receptor binding/activation potencies. Moreover, the marked anti-aggressive potency of F13714 adds additional support for a critical role of raphe somatodendritic 5-HT1A autoreceptors, and hence phasic 5-HT neuron activity, in the initiation/execution of aggressive actions.<p />  <p>Language: en</p>
LA  - en
SN  - 0033-3158
UR  - http://dx.doi.org/10.1007/s00213-015-4173-x
ID  - ref1
ER  -