NEUROTENSIN PEPTIDES ANTAGONISTICALLY REGULATE POSTSYNAPTIC DOPAMINE D-2 RECEPTORS IN RAT NUCLEUS-ACCUMBENS - A RECEPTOR-BINDING AND MICRODIALYSIS STUDY

An in vitro receptor binding and in vivo microdialysis study was perfo rmed to further investigate the modulation of dopamine (DA) D-2 recept ors by neurotensin (NT) peptides. Saturation experiments with the D-2 agonist [H-3]NPA (N-propylnorapomorphine) showed that 10 nM of NT, 10 nM of neuromedin N (NN) and 1 nM of the C-terminal NT-(8-13) fragment significantly increased the K-D values by 125%, 181%, and 194%, respec tively without significantly affecting the B-max value of the [H-3]NPA binding sites in coronal sections of rat ventral forebrain mainly con taining the nucleus accumbens (Acb) and the olfactory tubercle. In lin e with the previous findings that NT can increase GABA release in the Acb and that NT receptors are not found on DA terminals in this brain region, the present in vivo microdialysis study demonstrated that loca l perfusion of NT (1 nM) counteracted the D-2 agonist pergolide (2 mu M) induced inhibition of GABA, but not of DA release in the rat Acb. T his result indicates that NT counteracts the D-2 agonist induced inhib ition of GABA release in the rat Acb, via an antagonistic postsynaptic NT/D-2 receptor interaction as also suggested by the inhibitory regul ation of D-2 receptor affinity in the Acb by the NT peptides demonstra ted in the present. receptor binding experiments. Thus, the neurolepti c and potential antipsychotic profile of the NT peptides may involve a n antagonistic NT/D-2 receptor regulation in the ventral striatum.