CP 94253 hydrochloride

Regulation of extracellular concentrations of 5-hydroxytryptamine (5-HT) in mouse striatum by 5-HT(1A) and 5-HT(1B) receptors.[Pubmed:10688630]

J Pharmacol Exp Ther. 2000 Mar;292(3):1111-7.

The ability of selective serotonin (5-HT) receptor agonists to reduce the extracellular concentration of 5-HT was examined in the striatum of awake, unrestrained mice by in vivo microdialysis. Systemic administration of either 8-OH-PIPAT (R-(+)-trans-8-hydroxy-2-[N-n-propyl-N-(3'-iodo-2'-propenyl)] aminotetralin), a novel 5-HT(1A) receptor agonist, or CP 94,253, a selective 5-HT(1B) receptor agonist, resulted in significant dose-related reductions of striatal 5-HT. The effect of 8-OH-PIPAT (1.0 mg/kg) was blocked by pretreatment with WAY 100635 (0.1 mg/kg), a selective 5-HT(1A) receptor antagonist, but it was not blocked by pretreatment with GR 127935 (0.056 mg/kg), a selective 5-HT(1B/1D) receptor antagonist. The effect of CP 94,253 (1.0 mg/kg) was blocked by pretreatment with GR 127935 (0.056 mg/kg) but was not blocked by pretreatment with WAY 100635 (0.1 mg/kg). Neither WAY 100635 nor GR 127935 altered extracellular 5-HT levels at the doses that were able to completely block the effects of either 8-OH-PIPAT or CP 94,253. The present findings suggest that, on systemic administration, both 8-OH-PIPAT and CP 94,253 are potent and selective agonists at the somatodendritic 5-HT(1A) autoreceptor and terminal 5-HT(1B/1D) autoreceptor, respectively, and are each able to cause decreases in extracellular levels of 5-HT in the mouse striatum by activating a distinct set of receptors.

Aggression heightened by alcohol or social instigation in mice: reduction by the 5-HT(1B) receptor agonist CP-94,253.[Pubmed:10550489]

Psychopharmacology (Berl). 1999 Oct;146(4):391-9.

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(1B) selective agonist, CP-94,253, 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(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(1B) (GR 127935; 10 mg/kg, IP) and the 5-HT(1A) receptor (WAY 100,635; 0.1 mg/kg IP) were used. RESULTS: CP-94,253 suppressed non-heightened aggressive behavior (ED(50)=7.2 mg/kg ). GR 127935, but not WAY 100,635 shifted the ED(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(50)=3. 8 and 2.7 mg/kg, respectively). CONCLUSIONS: The current results support the hypothesis that activation of 5-HT(1B) receptors modulates very high levels of aggressive behavior in a pharmacologically and behaviorally specific manner.