Aggression heightened by alcohol or social instigation in mice: reduction by the 5-HT[sub 1B] receptor agonist CP-94,253.

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Bibliographic Details
Title:	Aggression heightened by alcohol or social instigation in mice: reduction by the 5-HT[sub 1B] receptor agonist CP-94,253.
Authors:	Fish, E. W., Faccidomo, S., Miczek, K. A.
Source:	Psychopharmacology. 1999, Vol. 146 Issue 4, p391. 9p.
Subjects:	Aggression (Psychology), Impulsive personality, Serotonin, Alcohol
Abstract:	Abstract Rationale: Models of heightened aggression may be particularly relevant in exploring pharmacological options for the clinical treatment of aggressive and impulsive disorders. Objectives: To investigate and compare the effects of a 5-HT[sub 1B] selective agonist, CP94,253, on aggression that was heightened as a result of 1) social instigation or 2) alcohol treatment. Methods: Male CFW mice were administered 1.0 g/kg EtOH and were subsequently confronted by an intruder in their home cage. In a separate experimental procedure, resident male mice were instigated to aggressive behavior by brief exposure to a provocative stimulus male. To test the hypothesis that activation of the 5-HT[sub 1B] receptor subtype would preferentially attenuate heightened aggression, in comparison to the moderate levels of species-typical aggressive behaviors, the selective agonist, CP-94,253 (1.0-30 mg/kg, IP), and antagonists to the 5-HT[sub 1B] (GR 127935; 10 mg/kg, IP) and the 5-HT[sub 1A] receptor (WAY 100,635; 0.1 mg/kg IP) were used. Results: CP-94,253 suppressed non-heightened aggressive behavior (ED[sub 50]=7.2 mg/kg). GR 127935, but not WAY 100,635 shifted the ED[sub 50] for CP-94,253 to 14.5 mg/kg. Importantly, the anti-aggressive effects of CP-94,253 were not accompanied by locomotor sedation. Alcohol-heightened and instigation-heightened aggression were suppressed at lower doses than those necessary to suppress non-heightened aggression (ED[sub 50]=3.8 and 2.7 mg/kg, respectively). Conclusions: The current results support the hypothesis that activation of 5-HT[sub 1B] receptors modulates very high levels of aggressive behavior in a pharmacologically and behaviorally specific manner. [ABSTRACT FROM AUTHOR]
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Database:	Psychology and Behavioral Sciences Collection

Description
Abstract:	Abstract Rationale: Models of heightened aggression may be particularly relevant in exploring pharmacological options for the clinical treatment of aggressive and impulsive disorders. Objectives: To investigate and compare the effects of a 5-HT[sub 1B] selective agonist, CP94,253, on aggression that was heightened as a result of 1) social instigation or 2) alcohol treatment. Methods: Male CFW mice were administered 1.0 g/kg EtOH and were subsequently confronted by an intruder in their home cage. In a separate experimental procedure, resident male mice were instigated to aggressive behavior by brief exposure to a provocative stimulus male. To test the hypothesis that activation of the 5-HT[sub 1B] receptor subtype would preferentially attenuate heightened aggression, in comparison to the moderate levels of species-typical aggressive behaviors, the selective agonist, CP-94,253 (1.0-30 mg/kg, IP), and antagonists to the 5-HT[sub 1B] (GR 127935; 10 mg/kg, IP) and the 5-HT[sub 1A] receptor (WAY 100,635; 0.1 mg/kg IP) were used. Results: CP-94,253 suppressed non-heightened aggressive behavior (ED[sub 50]=7.2 mg/kg). GR 127935, but not WAY 100,635 shifted the ED[sub 50] for CP-94,253 to 14.5 mg/kg. Importantly, the anti-aggressive effects of CP-94,253 were not accompanied by locomotor sedation. Alcohol-heightened and instigation-heightened aggression were suppressed at lower doses than those necessary to suppress non-heightened aggression (ED[sub 50]=3.8 and 2.7 mg/kg, respectively). Conclusions: The current results support the hypothesis that activation of 5-HT[sub 1B] receptors modulates very high levels of aggressive behavior in a pharmacologically and behaviorally specific manner. [ABSTRACT FROM AUTHOR]
ISSN:	00333158
DOI:	10.1007/PL00005484