Serotonergic Modulation of Agonistic Behaviour

Aggressive Behavior, Increased Accumbal Dopamine, and Decreased Cortical Serotonin in Rats

“…Indices of low serotonin activity in the brain have been associated with increased levels of aggression and violent behavior, as measured by decreased 5-HT in brain tissue in aggressive mice (Giacalone et al, 1968;Welch and Welch, 1968;Haney et al, 1990) and by decreased levels of 5-HIAA in CSF in violent humans (Brown et al, 1982;Linnoila et al, 1983;Kruesi et al, 1990;Coccaro, 1992;Virkkunen et al, 1996;Kavoussi et al, 1997) and aggressive macaques (Higley et al, 1992(Higley et al, , 1996Mehlman et al, 1994). Selective serotonergic agonists at the 5-HT 1A and 5-HT 1B receptor subtypes, as well as serotonin reuptake inhibitors, have been proven very effective in reducing aggressive behavior in rodents and humans (Olivier and Mos, 1986;Olivier et al, 1987;Miczek et al, 1998;de Boer et al, 1999;Ferris et al, 1999;Fish et al, 1999). However, CSF measurements and systemic pharmacological manipulations are removed from the critical neural sites of action.…”

“…In juvenile monkeys, low levels of 5-HIAA are correlated with increased risk-taking and impulsivity (Higley et al, 1992(Higley et al, , 1996Mehlman et al, 1994). If 5-HT undergoes dynamic state changes (Jacobs and Fornal, 1999) then in vivo measures would indicate whether altered serotonin actually is linked to the occurrence of episodes of aggression.In rodents, aggressive behavior is effectively reduced by treatment with 5-HT 1A and 5-HT 1B receptor agonists (Olivier and Mos, 1986;Olivier et al, 1987;De Almeida and Lucion, 1997;Simon et al, 1998;de Boer et al, 1999;Ferris et al, 1999;Fish et al, 1999). Furthermore, aggression is increased in 5-HT 1B receptor knock-out mice (Saudou et al, 1994).…”

“…In rodents, aggressive behavior is effectively reduced by treatment with 5-HT 1A and 5-HT 1B receptor agonists (Olivier and Mos, 1986;Olivier et al, 1987;De Almeida and Lucion, 1997;Simon et al, 1998;de Boer et al, 1999;Ferris et al, 1999;Fish et al, 1999). Furthermore, aggression is increased in 5-HT 1B receptor knock-out mice (Saudou et al, 1994).…”

Pharmacokinetics of eltoprazine in healthy male subjects after single dose oral and intravenous administration.

“…This action is exerted without impairment of sensory or motor functions and without sedation, in contrast with the actions of neuroleptics and other drugs used to suppress pathological destructive behaviour. The effects of serenics on aggression in animal experiments appear to be related to serotonergic (5-HTlA and 5-HT1B) activity (Bevan et al, 1990;Olivier et al, 1987Olivier et al, , 1990. Eltoprazine hydrochloride (hereinafter called eltoprazine) appears to be a mixed 5-HTlA/lB agonist, which exerts specific anti-aggressive effects in several aggression paradigms in animals (Bevan et al, 1990;Olivier etal., 1987).…”

Serotonergic modulation of social interactions in isolated male mice

“…Studies of the mechanism of action of serenics strongly suggested that their specific anti-aggressive action was caused by an interaction with 5-HT1 receptors (Olivier et al 1987), and more specifically with a subtype, the 5-HT1B site. Because several 5-HT receptor sites are known, including 5-HTt(A,B,C,D), 5-HT2 and 5-HTa(A,B,C), and receptor-specific pharmacological tools (agonists and antagonists) are becoming available, it is feasible to explore specific 5-HT~B involvement in aggression by studying the behavioral effects of specific serotonergic drugs on agonistic behavior.…”