Enhanced Aggressive Behavior in Mice Lacking 5-HT _1B Receptor

Abstract

The neuromodulator serotonin (5-hydroxytryptamine, 5-HT) has been associated with mood disorders such as depression, anxiety, and impulsive violence. To define the contribution of 5-HT receptor subtypes to behavior, mutant mice lacking the 5-HT1B receptor were generated by homologous recombination. These mice did not exhibit any obvious developmental or behavioral defects. However, the hyperlocomotor effect of the 5-HT1A/1B agonist RU24969 was absent in mutant mice, indicating that this effect is mediated by 5-HT1B receptors. Moreover, when confronted with an intruder, mutant mice attacked the intruder faster and more intensely than did wild-type mice, suggesting the participation of 5-HT1B receptors in aggressive behavior.

5-HT1A/1B Receptor-Mediated Effects of the Selective Serotonin Reuptake Inhibitor, Citalopram, on Sleep: Studies in 5-HT1A and 5-HT1B Knockout Mice

“…All mice were of the same 129/Sv genetic background. They were produced in the laboratory from homozygous breeding of wild-type and mutant (5-HT 1A À/À and 5-HT 1B À/À) strains (Saudou et al, 1994;Ramboz et al, 1998;Boutrel et al, 1999Boutrel et al, , 2002, and housed in standard animal care facilities (see below).…”

“…These considerations led us to address this question by using knockout mice that do not express 5-HT 1A or 5-HT 1B receptors (Saudou et al, 1994;Ramboz et al, 1998). We analyzed the effects of citalopram, the most selective SSRI currently available (Hyttel, 1982;Milne and Goa, 1991), on sleep-wakefulness cycles in 5-HT 1A and 5-HT 1B knockout mice and their wild-type counterparts.…”

Exploration of 19 serotoninergic candidate genes in adults and children with attention-deficit/hyperactivity disorder identifies association for 5HT2A, DDC and MAOB

“…Once administered, serotonin agonists, which include 5-hydroxytryptophan, L-tryptophan and selective serotonin reuptake inhibitors, markedly attenuate hyperactivity in the DAT-KO mice. 34 In addition, mice lacking the 5HT1B receptor show hyperactivity, increased aggression and behavioral deinhibition [35][36][37][38][39] and 5HT4 receptor knockout mice show attenuated novelty-induced exploratory activity. 40 Finally, 5HT2 receptor agonists modulate hyperlocomotor activity in rats, and monoamine oxidase inhibitors reduce impulsiveness in animal models of ADHD.…”

Knockout Mice Reveal Opposite Roles for Serotonin 1A and 1B Receptors in Prepulse Inhibition

“…5-HT 1B receptors are most densely localized on striatal neuron terminals in the globus pallidus and substantia nigra, and on Purkinje neuron terminals in the deep cerebellar nuclei (Boschert et al 1994;Pazos et al 1988). Many of these brain regions, such as the hippocampus (Caine et al 1991), septum (Koch 1996, raphe (Sipes and Geyer 1995), and ventral pallidum (Swerdlow et al 1990(Swerdlow et al , 1992Sipes and Geyer 1997), are components of the neural circuitry involved in modulating PPI.We assessed the roles of 5-HT 1A and 5-HT 1B receptors in modulating PPI and habituation using WT, 1AKO, and 1BKO mice, which are without any obvious anatomical or behavioral abnormalities (Ramboz et al 1998;Saudou et al 1994). WT, 1AKO, and 1BKO mice received saline, the 5-HT 1A/1B agonist RU24969, which binds preferentially at 5-HT 1B sites (Sills et al 1984;Doods et al 1985), and the 5-HT 1A agonist 8-OH-DPAT.…”

“…We assessed the roles of 5-HT 1A and 5-HT 1B receptors in modulating PPI and habituation using WT, 1AKO, and 1BKO mice, which are without any obvious anatomical or behavioral abnormalities (Ramboz et al 1998;Saudou et al 1994). WT, 1AKO, and 1BKO mice received saline, the 5-HT 1A/1B agonist RU24969, which binds preferentially at 5-HT 1B sites (Sills et al 1984;Doods et al 1985), and the 5-HT 1A agonist 8-OH-DPAT.…”