Effect of dihydroergosine (DHESN) on the serotoninergic system and behaviour: is DHESN a new antidepressive agent?
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.
D000818:Animals; D000928:Antidepressive Agents; D001792:Blood Platelets / Q000378:metabolism; D003533:Cyproheptadine / Q000494:pharmacology; D004879:Ergotamines / Q000494:pharmacology*; D010134:Fenclonine / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000097:blood / Q000502:physiology*
D000928:Antidepressive Agents; D004879:Ergotamines; D008996:Monoamine Oxidase Inhibitors; D003533:Cyproheptadine; D012701:Serotonin; C037580:9,10-dihydroergosine; D006220:Haloperidol; D011339:Probenecid; D010134:Fenclonine