DIHYDROERGOSINE - ANTICONFLICT EFFECT IN RATS AND ENHANCING EFFECTS ON [H-3] MUSCIMOL BINDING IN THE HUMAN BRAIN POSTMORTEM

The anticonflict activity of the ergot alkaloid, dihydroergosine, a dr ug which binds to 5-hydroxytryptamine1 (5-HT1) receptors and to gamma- aminobutyric acid, (GABA(A)) receptor-associated Cl- ionophore, was st udied in water-deprived rats. In vitro effects of this drug on [H-3]mu scimol and [H-3]flunitrazepam binding to the crude synaptosomal pellet of the human frontal cortex post-mortem were also investigated. Dihyd roergosine, given 2 h prior to testing, enhanced drinking under punish ed (0.8 mA) conditions, and diminished it under unpunished conditions. The mechanism of this effect was (-)-propranolol- and pindolol-insens itive and picrotoxin-sensitive. Flumazenil either failed to affect, or at a higher dose (10 mg/kg), counteracted the dihydroergosine-induced enhancement of punished drinking. This dose of flumazenil was itself anxiogenic. Dihydroergosine had mild sedative and analgesic properties . Low concentrations of dihydroergosine (10 nM to 100 muM) enhanced th e binding of [H-3]muscimol but not of [H-3]flunitrazepam. The results suggest that dihydroergosine may possess anxiolytic properties presuma bly mediated by its specific action at the GABA/benzodiazepine/chlorid e channel complex.