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Behav Brain Res. 2013 Nov 1;256:354-61. doi: 10.1016/j.bbr.2013.07.044. Epub 2013 Aug 6.

Serotonin₂A/C receptors mediate the aggressive phenotype of TLX gene knockout mice.

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  • 1Department of Special Education, Vanderbilt University, Nashville, TN, USA.


Deleting the tailless (TLX) gene in mice produces a highly aggressive phenotype yet to be characterized in terms of heterozygous animals or neurotransmitter mechanisms. We sought to establish pharmacological control over aggression and study the role of serotonin (5-HT)(2A/C) receptors in mediating changes in aggression. We analyzed aggression in mice heterozygous (+/-) or homozygous (-/-) for the TLX gene and wild-types (+/+) using a resident-intruder paradigm. No +/+ mice were aggressive, 36% of +/- TLX and 100% of -/- TLX mice showed aggression. Dose-effect functions were established for clozapine (0.1-1.5mg/kg, ip), ketanserin (0.3-1.25 mg/kg, ip), and (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane [(±)DOI] (0.5-2.0 mg/kg, ip). Injecting clozapine decreased the frequency and duration of attacks for +/- TLX and -/- TLX mice. Clozapine did not decrease grooming in either +/- TLX or -/- TLX mice but may have increased locomotion for -/- TLX mice. Injecting ketanserin, a 5-HT(2A/C) receptor antagonist, produced differential decreases in frequency and latency to aggression between genotypes and corresponding increases in locomotor behavior. Injecting (±)DOI, a 5-HT(2A/C) receptor agonist, increased the frequency and duration of attacks, decreased the latency to attacks, and decreased locomotion in +/- and -/- TLX mice. Results of the current study suggest aggression displayed by TLX null and heterozygous mice involves 5-HT(2A/C) receptors.

Copyright © 2013 Elsevier B.V. All rights reserved.


(±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane; (±)DOI; 5-HT; 5-HT(2A/C) receptors; Aggression; Fierce; Resident-intruder; Serotonin; TLX; TLX gene; tailless

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