Antidepressant-like effect of the selective 5-HT1B receptor agonist CP 94253: a possible mechanism of action.
The mechanism of the antidepressant-like activity of the selective 5-hydroxytryptamine(1B) (5-HT(1B)) receptor agonist 5-propoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-pyrrolo[3,2-b]pyridine (CP 94253) was studied in the forced swimming test in mice. CP 94253 administered intraperitoneally at a single dose of 5 mg/kg potently shortened the immobility time of mice. The anti-immobility effect of CP 94253 was wholly blocked by the selective 5-HT(1B) receptor antagonist N-[3-(2-dimethylamino)ethoxy-4-methoxyphenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-(1,1'-biphenyl)-4-carboxamide (SB 216641, 5 mg/kg), the dopamine D2-like receptor antagonist sulpiride (50 mg/kg) and the alpha(2)-adrenoceptor antagonist idazoxan (2 mg/kg), but was not modified in animals with a lesion of the 5-HT system produced by p-chlorophenylalanine (p-CPA, 3 x 300 mg/kg). The obtained results suggest that the anti-immobility effect of CP 94253 is mediated by activation of 5-HT(1B) receptors-most probably located postsynaptically and/or as heteroreceptors, and that the dopamine and the noradrenaline systems are involved in this action.
Tatarczyńska
Ewa
E
Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, Cracow PL 31-343, Poland.
Antkiewicz-Michaluk
Lucyna
L
Kłodzińska
Aleksandra
A
Stachowicz
Katarzyna
K
Chojnacka-Wójcik
Ewa
E
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D010134:Fenclonine / Q000494:pharmacology; D019329:Idazoxan / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010069:Oxadiazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D044302:Receptor, Serotonin, 5-HT1B / Q000502:physiology; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013469:Sulpiride / Q000494:pharmacology; D013550:Swimming
D000317:Adrenergic alpha-Antagonists; D000928:Antidepressive Agents; D001549:Benzamides; C097067:CP 94253; D018492:Dopamine Antagonists; C108531:N-(3-(2-dimethylamino)ethoxy-4-methoxyphenyl)-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-(1,1'-biphenyl)-4-carboxamide; D010069:Oxadiazoles; D011725:Pyridines; D044302:Receptor, Serotonin, 5-HT1B; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013469:Sulpiride; D010134:Fenclonine; D019329:Idazoxan