5-HT4 RECEPTOR INVOLVEMENT IN THE SEROTONIN-ENHANCED DOPAMINE EFFLUX FROM THE SUBSTANTIA-NIGRA OF THE FREELY MOVING RAT - A MICRODIALYSIS STUDY

The functional regulation by serotonin (5-HT) receptors of the 5-HT-en hanced dopamine (DA) release from the rat substantia nigra (SN) was in vestigated using in vivo microdialysis. Exogenously administered or ex tracellularly enhanced 5-HT (by means of intranigral citalopram perfus ion) (both 1 mu M for 1 h) significantly increased nigral DA efflux to 165% and 145%, respectively. Intranigral administration of pindolol ( 10 mu M, 3 h), a 5-HT1A/1B receptor antagonist which is clinically use d in order to block 5-HT1A/1B autoreceptors, did not affect DA levels but significantly increased nigral 5-HT levels to 135%. Co-perfusion o f this antagonist with 5-HT (1 mu M, 1 h) did not abolish the 5-HT-ind uced DA release from the SN as DA was increased to 165%. Local applica tion of the 5-HT1A/1B receptor agonist, CP 93129 (1 mu M, 1 h), increa sed DA release from the SN to 4770% whereas 5-HT release was significa ntly decreased to 75%. Co-perfusion of the 5-HT1A/1B receptor antagoni st, pindolol, with this agonist only partly abolished the CP 93129-ind uced DA release whereas the CP 93129-induced decrease in nigral 5-HT r elease was completely abolished. Administration of the 5-HT2A/2C recep tor antagonist, ketanserin (50 mu M, 3 h), significantly increased DA to 143% acid 5-HT release to 363%. Co-perfusion of this antagonist wit h 5-HT still caused an increase in nigral DA release to 214%. Intranig ral perfusion of the 5-HT4 receptor antagonist, RS 39604 (10 mu M, 3 h ), did not affect DA levels but significantly decreased nigral 5-HT le vels to 74%. Co-perfusion of this antagonist with 5-HT was able to pre vent the 5-HT-enhanced DA efflux from the SN. From this study it can b e concluded that the 5-HT-enhanced (and possibly the citalopram-induce d) nigral DA release is 5-HT4 receptor mediated. (C) 1998 Elsevier Sci ence B.V. All rights reserved.