THE LIMBIC FUNCTIONAL SELECTIVITY OF AMPEROZIDE IS NOT MEDIATED BY DOPAMINE D-2 RECEPTORS AS ASSESSED BY IN-VITRO AND IN-VIVO BINDING

Behavioural, biochemical and electrophysiological studies suggest that amperozide affects mesolimbic dopamine neurotransmission. Amperozide is a potent 5-HT2 receptor antagonist with only a moderate affinity fo r rat brain dopamine D-2 receptors. The brain regional dopamine D-2 re ceptor binding properties of amperozide were investigated by using in vitro and in vivo radioligand binding techniques. Amperozide displaced [H-3]spiroperidol binding from rat striatal and limbic dopamine D-2 r eceptors with moderate affinity (K-i = 540 +/- 118 nM and K-i = 403 +/ - 84 nM, respectively). The dopamine D-2 receptor antagonist l-sulpiri de and the agonist dopamine did not show different affinity in the two brain regions. Amperozide potently displaced in vivo [H-3]spiroperido l binding in rat frontal cortex (ID50 = 1.4 mg/kg s.c.) but was devoid of effect in striatum, olfactory tubercle and nucleus accumbens (ID50 > 100 mg/kg s.c.). Chronic administration of amperozide (5 mg/kg p.o. ) for three weeks did not result in any change of maximal dopamine D-2 receptor number in either striatal or limbic tissue. The effects of a mperozide on dopamine neurotransmission are thus not likely to occur b y a direct interaction with dopamine D-2 receptors in either striatal or limbic tissue. The functional limbic selectivity might rather be me diated by serotoninergic pathways.