Blockade of the serotonergic system counteracts the dizocilpine-induced changes in dopaminergic function

The administration of dizocilpine, a non-competitive N-methyl-D-aspartate ( NMDA) receptor antagonist acting at the associated ion channel, increased t he grooming time induced in rats by the D-1 dopamine receptor agonist SKF 3 8393 and the stereotyped behaviour elicited by the D-1/D-2 dopamine recepto r agonist apomorphine, and reduced the locomotor response to the D-2 dopami ne receptor agonist quinpirole. This supports the view that glutamate defic iency plays an important role in the pathogenesis of schizophrenia by alter ing the balance between glutamatergic and dopaminergic systems. Blockade of serotonin receptors counteracted the effect of dizocilpine on dopaminergic responses. Both the non-selective 5HT(1)/5HT(2) antagonist methysergide, a nd ketanserin, which more specifically blocks 5HT(2) receptors, given at do ses inhibiting serotonin-mediated behaviours but which did not affect spont aneous motility and dopaminergic behaviours, hampered the dizocilpine-induc ed potentiation of responses elicited by the stimulation of D-1 or D-1/D-2 dopamine receptors and counteracted the dizocilpine-induced reduction of hy peractivity observed following quinpirole administration. The results sugge st that the functional integrity of the serotonergic system is fundamental for the occurrence of dopaminergic changes resulting from non-competitive N MDA blockade. (C) 2000 Lippincott Williams & Wilkins.