The influence of ACEA--a selective cannabinoid CB1 receptor agonist on whole blood and platelet-poor plasma serotonin...

Through the CB1 receptor cannabinoids modulate serotonin (5-hydroxytryptamine, 5-HT) release in the central nervous system which is connected with some of their pharmacological effects, especially antidepressant activity. 5-HT has many important physiological functions also in the periphery, particularly in the circulatory system and digestive tract. 5-HT dysfunction may be involved in some diseases pathogenesis including hypertension, migraine, cardiac disorders, cerebral ischemia or peripheral vascular diseases. Cannabinoids possible influence on 5-HT release in peripheral tissues may be clinically significant. The aim of the present study was to investigate the influence of ACEA (arachidonyl-2-chloroethylamide), a selective cannabinoid CB1 receptor agonist on whole blood (WB) and platelet-poor plasma (PPP) 5-HT levels. The experiments were carried out on male and female Wistar rats. ACEA (3 mg/kg i.p.) was given alone and in combination with a selective CB1 receptor antagonist AM 251 (3 mg/kg i.p.). Concentrations of 5-HT in WB and PPP were determined by enzyme-linked immunosorbent assay (Serotonin ELISA). ACEA significantly decreased concentration of 5-HT in WB (to 61%, p < 0.02) and its effect was blocked by AM 251. ACEA also reduced of 5-HT in PPP (to 62%) however, the difference was statistically insignificant. Research results reveal that due to CB1 receptor stimulation, ACEA reduces 5-HT contents in bloodstream. This effect is probably the result of inhibition of 5-HT release from gastrointestinal tract.