Zolmitriptan - a 5-HT 1B/D agonist, alcohol, and aggression in mice

Abstract

Zolmitriptan proved to be an effective and behaviorally specific anti-aggressive agent in situations that engender moderate and alcohol-heightened levels of aggression. These effects are potentially due to activation of post-synaptic 5-HT1BD receptors.

Escalated Aggression after Alcohol Drinking in Male Mice: Dorsal Raphé and Prefrontal Cortex Serotonin and 5-HT1B Receptors

“…In conclusion, one of the most consistent findings in aggression research is that 5-HT agonists decrease aggressive behavior in multiple species, under various conditions involving receptors in the 5-HT 1 and 5-HT 2 families (Olivier and Mos, 1986;Sanchez et al, 1993;Muehlenkamp et al, 1995;Miczek et al, 1998Miczek et al, , 2007Fish et al, 1999;de Almeida et al, 2001). The heightened aggressive behavior that we have shown after medial prefrontal microinjection of CP-94,253 is intriguing because it (1) further confirms that the 5-HT 1B receptor is one of the few receptors that specifically modulates aggressive behavior and (2) reveals that selective increases in aggressive behavior are possible via a serotonergic mechanism.…”

“…Inactivation of somatodendritic 5-HT 1B receptors by intraraphé 5,7-DHT or PCPA injections fails to attenuate the antiaggressive-and antidepressant-like effects of 5-HT 1B agonists, suggesting that these behaviors are modulated by post-synaptic 5-HT 1B heteroreceptor activity (Clark and Neumaier, 2001;de Almeida et al, 2001;Tatarczyñska et al, 2005). Local administration of 5-HT 1B agonists decreases extracellular levels of glutamate in the prefrontal cortex, which, presumably, is due to activation of 5-HT 1B receptors located on cortical glutamatergic neurons (Gołembiowska and Dziubina, 2002).…”

Aggression Escalated by Social Instigation or by Discontinuation of Reinforcement (“Frustration”) in Mice Inhibition by Anpirtoline: A 5-HT1B Receptor Agonist

“…Similarly, correlation of aggressive behavior with a single tissue or CSF measurement of serotonin or its metabolite need to be reconciled with the anti-aggressive effects of agonist NO . 2 and antagonist treatment of specific serotonin receptor subtypes (Olivier et al 1995;de Almeida et al 2001).The exposure of an experimental subject to a potential rival for a short time prior to the actual confrontation engenders intense levels of aggression, as originally described in mice (Lagerspetz 1969;Tellegen and Horn 1972). For example, mice, rats, and hamsters initiate attacks with very short latency and at high frequency when tested with an intruder in their home cage or in an unfamiliar locale after having been provoked previously by an opponent (Potegal 1992;Fish et al 1999).…”

“…The present experiments attempt to study extinction-induced aggression in mice, a species that has become of considerable interest because of developments in molecular genetics ). Whether or not heightened aggression resulting from discontinued reinforcement is characterized by a distinctive profile of serotonergic activity remains to be explored.Activation and antagonism of several 5-HT receptor subtypes in the 5-HT 1 and 5-HT 2 families suppress aggressive behavior (Sanchez et al 1993;de Almeida and Lucion 1994;Olivier et al 1995;de Almeida and Lucion 1997;Miczek et al 1998;de Almeida et al 2001). Experimental deletion of the gene coding for the 5-HT 1B receptor as well as pharmacological studies implicate this receptor subtype in aggressive behavior (Saudou et al 1994;Mos et al 1992).…”

Interaction of nitric oxide and serotonin in aggressive behavior

“…Drugs that inhibit 5-HT synthesis such as parachlorophenylalanine (pCPA), a tryptophan-free diet, and lesions of 5-HT neurons decrease 5-HT levels and elevate aggression in nonhuman animals (Hole et al, 1977;Gibbons et al, 1978Gibbons et al, , 1979Valzelli et al, 1981;Chiavegatto et al, 2001). Conversely, reduction in aggression has been obtained by treatment with 5-HT precursors, 5-HT reuptake inhibitors, 5-HT releasing agents, in addition to 5-HT 1A and 5-HT 1B agonists (Gibbons et al, 1978(Gibbons et al, , 1981Rolinski and Herbut, 1981;Olivier et al, 1995;Chiavegatto et al, 2001;Miczek and de Almeida, 2001;de Almeida et al, 2001).…”