Involvement of the serotonergic system in the prolongation of pentobarbital sleeping time produced by prostaglandin D2.

In the present study, the depressant and sedative actions of prostaglandin D2 (PGD2) were investigated. Intravenous (IV) administration of PGD2 produced a significant decrease in the spontaneous locomotor activity of mice from 1 to 15 minutes following injection. Prostaglandin D2 was also able to potentiate pentobarbital sleeping time at doses of 0.4 and 4.0 mg/kg when administered intravenously. Distribution studies with 3H-PGD2 (6 microCi, 4 mg/kg) showed that only 0.04% of the tritium administered could be found in brain at 5 min after the injection, and that only 50% of this was parent 3H-PGD2. The role of the serotonergic neurotransmitter system in the depressant action of PGD2 was investigated with drugs which modulate this system. The ability of PGD2 to potentiate pentobarbital sleeping time was diminished by pretreatment with agents that reduce brain level or synthesis rate of serotonin. Such agents include para-chlorophenylalanine (PCPA), a tryptophan hydroxylase inhibitor, 5,7-dihydroxytryptamine (5,7-DHT), a neurotoxin with selectivity for serotonergic neurons, and quipazine, a serotonergic autoreceptor stimulant. On the other hand, pretreatment with 5-hydroxytryptophan (5-HTP), the precursor of serotonin, further enhanced the potentiation of pentobarbital sleeping time by PGD2. These data suggest that the depressant actions of PGD2 are linked to the serotonergic neurotransmitter system.