Serotonergic modulation of rat pineal gland activity: In vivo evidence fora 5-hydroxytryptamine(2C) receptor involvement

There are some suggestions that, in the pineal gland, serotonin acts not on ly as a precursor of melatonin but also plays a role in the modulation of t he pineal biosynthetic activity. To corroborate this possible neuromodulato ry role of 5-hydroxytryptamine (serotonin) (5-HT) on the pineal gland, the effects of two 5-HT2 receptor agonists meta-chlorophenylpiperazine (m-CPP) and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane were assessed in vivo on pineal N-acetyltransferase (NAT) activity and melatonin content in rats. m- CPP potentiated the enhancement of NAT activity and pineal melatonin conten t induced by isoproterenol administration during daytime, whereas it did no t affect the diurnal basal biosynthetic activity of the gland. At night, m- CPP and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane enhanced significantl y the physiological increases in both pineal NAT activity and melatonin con tent. This enhancement was prevented by pretreatment with N-(1-methyl-5-ind olyl)-N'-(3-pyridyl) urea hydrochloride, an antagonist with higher affinity for 5-HT2B/C than for 5-HT2A receptor, as well as by pretreatment with 8-[ 5-(2,4-dimethoxy-5-(4-trifluoromethyl-phenylsulphonamido)-phenyl-5-oxopenth yl]-1,3,8-triazospiro[4,5]decane-2,4-dione, the most specific 5-HT2C recept or now available, but not by pretreatment with ketanserin, an antagonist wi th higher affinity for 5-HT2A than for 5-HT2C receptor. These results sugge st that 5-HT2C receptors are likely involved in the mediation of the seroto nergic modulation of pineal biosynthetic activity in rats.