Effects of the 5-HT3 receptor antagonist, GR38032F, on raised dopaminergic activity in the mesolimbic system of the rat and marmoset brain.

摘要: 1 The ability of the selective 5-HT3 receptor antagonist GR38032F to reduce raised mesolimbic dopaminergic activity was studied in behavioural experiments rat and marmoset. 2 injected into nucleus accumbens (0.01-1 ng) or peripherally mg kg-1 i.p.) inhibited locomotor hyperactivity caused by acute intra-accumbens injection amphetamine (10 micrograms) rat. Similar treatments with sulpiride fluphenazine also amphetamine-induced hyperactivity. 3 peripheral administration (0.001-0.1 i.p., b.d.) during a 13 day period dopamine infusion (25 micrograms 24 h-1) reduced dopamine-induced response control (vehicle infused) levels. Locomotor remained at levels after discontinuing dopamine/GR38032F treatment regimen. 4 (0.01-0.05 b.d.), but suppressed below values rebound occurred discontinuation dopamine/fluphenazine 5 concomitant haloperidol, 0.01 i.p.t.d.s., This i.p.). 6 unilateral h-1, days) left amygdala rats having right hemispheric dominance (as measured turn preference test) Intraperitoneal (0.1-100 kg-1) (0.025-0.1 kg-1), intra-amygdaloid (25-500 pg), either infused non-infused side, 7 Marmosets receiving bilaterial infusions h-1 for exhibited increased activity, (0.1-1.0 t.d.s.), no following Fluphenazine (0.01-2.5 t.d.s.) hyperactivity, followed treatment. 8. It is concluded that GR38032F, neuroleptic agents fluphenazine, can distinguished from antagonists by, firstly, its return values, without excessive suppression locomotion even on enhanced dosage regimes and, secondly, lack abrupt