Effect of dihydroergosine (DHESN) on the serotoninergic system and behaviour: Is DHESN a new antidepressive agent?

Abstract

Acute (50.0 mg/kg) and repeated (0.1-10.0 mg/kg) administration of dihydroergosine (DHESN) to rats over 5 days lowered the concentration of 5-HIAA in the brain. DHESN given acutely increased the brain 5-HT in p-CPA-treated animals and diminished the probenecid-induced increase in brain 5-HIAA. In pargyline-treated rats DHESN enhanced the 5-HT/5-HIAA ratio. DHESN administered to rats repeatedly over 5 days decreased the level of 5-HT in blood platelets, and in vitro at concentrations of 10(-4) M and 10(-3) M inhibited the uptake of [14C]-5-HT in platelets. DHESN (10.0-100.0 mg/kg) potentiated the 5-HT syndrome produced in rats by pargyline and 5-HTP. This potentiation was blocked with cyproheptadine but not with haloperidol. DHESN (1.0 and 10.0 mg/kg) lowered the locomotor activity of rats and 10.0 mg/kg DHESN also reduced the duration of immobility in rats forced to swim in a restricted space. The results indicate that DHESN, like antidepressants, decreases the turnover of serotonin in the brain and potentiates the 5-HT-mediated behaviour. This might suggest that the drug should be further investigated for its potential antidepressive properties.

Possible antidepressant dihydroergosine preferentially binds to 5-HT1B receptor sites in the rat hippocampus

“…Thus, we have shown that dihydroergosine stimulates the 5-HT syndrome in rats Manev, 1987, 1988;Peri~i6 and Muck-Seler, 1990), inhibits the head-twitch behavior in rats and mice (Peri~i6 and Manev, 1988;Peri~i6 and Muck-Seler, 1990), possesses antiaggressive properties in two models of isolation induced aggressiveness (Manev et al, 1989), and produces a shortening of immobility in the forced swimm test (Manev and Peri~i6, 1988). Biochemical changes observed in the rat brain after administration of dihydroergosine also indicate the involvement of the 5-HT system (Peri~i6 et al, 1986). Recently, on the base of the behavioral studies we have suggested that both the classic antidepressant imipramine, and a possible antidepressant dihydroergosine-possess two components-one stimulating the 5-HT syndrome in rats, presumably by a 5-HT1 A-mediated mechanism, and the other inhibiting 5-HT 2 binding sites (Peri~i6 and Muck-Seler, 1990).…”

“…Studies conducted in our laboratory have revealed that the ergot alkaloid dihydroergosine affects central serotoninergic transmission. On the basis of biochemical and behavioural experiments we have suggested that this drug might be a new antidepressant (Peri~i6 et al, 1986;Peri~i6 and Manev, 1987;Manev and Peri~i6, 1988). Thus, we have shown that dihydroergosine stimulates the 5-HT syndrome in rats Manev, 1987, 1988;Peri~i6 and Muck-Seler, 1990), inhibits the head-twitch behavior in rats and mice (Peri~i6 and Manev, 1988;Peri~i6 and Muck-Seler, 1990), possesses antiaggressive properties in two models of isolation induced aggressiveness (Manev et al, 1989), and produces a shortening of immobility in the forced swimm test (Manev and Peri~i6, 1988).…”

Dual species dependent effect of dihydroergosine on the convulsions induced by GABA antagonists

“…Dihydroergosine has been shown to decrease the turnover of serotonin (5-HT) in the whole brain (Peri6i6 et al, 1986b), to potentiate long-lastingly the 5-HT syndrome in the rat Manev, 1987, 1988) and to inhibit the headtwitch response in rats and mice . Recently, some neuropharmacological properties of this substance have been discovered.…”