ergoline and 1-(2-(diphenylmethoxy)ethyl)-4-(3-phenyl-2-propenyl)piperazine

The acute effects of increasing doses of the antidepressant drugs amineptine (5-40 mg/kg, IP) and desipramine (5-20 mg/kg IP) were studied in mice on three parameters of the activity (the horizontal activity, the vertical activity and the number of small movements without displacement) measured in a computerized Digiscan actimeter. The horizontal and vertical activities were dose dependently and similarly increased by acute amineptine, whereas the number of movements without displacement was increased up to 10 mg/kg with no further significant modification up to 40 mg/kg; in contrast, all three parameters were reduced in an identical manner by desipramine. The changes in the responses to the selective D-1 dopamine (DA) receptor agonist SK&F 38393 (1.87-30 mg/kg, SC), to the selective D-2 DA receptor agonist LY 171555 (0.1-1.6 mg/kg, SC) and to the selective DA uptake inhibitor GBR 12783 (1.25-20 mg/kg, IP) were measured on the three parameters of activity in mice chronically treated with amineptine (20 mg/kg, IP twice daily during 15 days) or by desipramine (10 mg/kg, IP, twice daily during 15 days). The chronic treatments with amineptine or desipramine did not modify the motor stimulant effects GBR 12783 and of SK&F 38393 on the three parameters (excepted for a slight modification of the horizontal activity for 7.5 mg/kg SK&F 38393 in mice chronically treated with amineptine). In contrast, the motor inhibitory effects of the lowest doses of LY 171555 (0.1-0.4 mg/kg) were strongly reduced in mice chronically treated with amineptine or desipramine but only on the horizontal activity with no change on the vertical activity and on the number of small movements without displacement.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Animals; Central Nervous System Stimulants; Desipramine; Dibenzocycloheptenes; Dopamine; Dopamine Agents; Dose-Response Relationship, Drug; Ergolines; Male; Mice; Motor Activity; Piperazines; Psychomotor Performance; Quinpirole

The effects of various dopaminergic drugs on the spontaneous and veratrine-stimulated release of endogenous dopamine (DA) from superfused rat striatal slices have been examined using a high-sensitivity HPLC system. The DA uptake inhibitor nomifensine greatly increased both veratrine-stimulated and spontaneous DA release, whilst the effects of the more potent and selective inhibitor GBR 12921 were much smaller. The DA agonists pergolide and LY 171555 reduced both spontaneous and veratrine-stimulated DA release; conversely, the D-2 selective antagonist l-sulpiride stereospecifically increased spontaneous and veratrine-stimulated release, and blocked the effects of pergolide and LY 171555. Inhibition of DA synthesis did not directly influence the actions of either pergolide or sulpiride. These studies indicate that nomifensine may have a DA-releasing action in addition to its uptake blocking action, the regulation of endogenous DA release by D-2 autoreceptors shows properties similar to those reported previously for radiolabelled DA release, with the novel finding that spontaneous release is also regulated, the autoreceptors do not appear to selectively influence newly synthesised DA release.

Topics: Animals; Calcium; Chromatography, High Pressure Liquid; Corpus Striatum; Dopamine; Dopamine Antagonists; Ergolines; In Vitro Techniques; Male; Methyltyrosines; Nomifensine; Piperazines; Quinpirole; Rats; Rats, Inbred Strains; Receptors, Dopamine; Tetrodotoxin