SIMULTANEOUS QUANTIFICATION OF SEROTONIN, DOPAMINE AND NORADRENALINE LEVELS IN SINGLE FRONTAL-CORTEX DIALYSATES OF FREELY-MOVING RATS REVEALS A COMPLEX PATTERN OF RECIPROCAL AUTO-MEDIATED AND HETERORECEPTOR-MEDIATED CONTROL OF RELEASE

In the present study, a novel and exceptionally sensitive method of hi gh-performance liquid chromatography coupled to coulometric detection, together with concentric dialysis probes, was exploited for an examin ation of the role of autoreceptors and heteroceptors in the modulation of dopamine, noradrenaline and serotonin levels in single samples of the frontal cortex of freely-moving rats. The selective D-3/D-2 recept or agonist, CGS 15855A ,3,4,4a,5,10b-hexahydro-4-propyl-2H-[1]benzopyr ano [3,4-b]-pyridin-9-ol], and antagonist, raclopride, respectively de creased (-50%) and increased (+60%) levels of dopamine without signifi cantly modifying those of serotonin and noradrenaline. The selective a lpha(2)-adrenergic receptor agonist, dexmedetomidine, markedly decreas ed noradrenaline levels (-100%) and likewise suppressed those of serot onin and dopamine by -55 and -45%, respectively. This effect was mimic ked by the preferential alpha(2A)-adrenergic receptor agonist, guanabe nz (-100%, -60% and -50%). Furthermore, the alpha(2)-adrenergic recept or antagonist, RX 821,002 [2(2-methoxy- 1,4-benzodioxan-2-yl)-2-imidaz oline], and the preferential alpha(2A)-adrenergic receptor antagonist, BRL 44405 ,3-dihydroisoindole)methyl)-4,5-dihydroimidazole], both evo ked a pronounced elevation in levels of noradrenaline (+212%, +109%) a nd dopamine (+73%, +85%). In contrast, the preferential alpha(2B/2C)-a drenergic receptor antagonist, prazosin, did not modify noradrenaline and dopamine levels. RX 821,002 and BRL 44408 did not significantly mo dify levels of serotonin, whereas prazosin decreased these levels mark edly (-55%), likely due to its alpha(1)-adrenergic receptor antagonist properties. The selective serotonin-1A receptor agonist, 8-hydroxy-2- (di-n-propylamino)-tetralin (8-OH-DPAT), reduced serotonin levels (-65 %) and increased those of dopamine and noradrenaline by +100% and +175 %, respectively. The selective serotonin-1A antagonist, WAY 100,635 [N -[2-[4-(2-methoxyphenyl)- yl]ethyl]-N-(2-pyridinyl)cyclo-hexanecarboxa mide], which had little affect on monoamine levels alone, abolished th e influence of 8-OH-DPAT upon serotonin and dopamine levels and signif icantly attenuated its influence upon noradrenaline levels. Finally, t he selective serotonin-1B agonist, GR 46611 [3-[3-(2-dimethylaminoethy l)-1H-indol-5-yl]-N- (4-methoxybenzyl)acrylamide], decreased serotonin levels (-49%) and the serotonin-1B antagonist, GR 127,935 [N-[4-metho xy- perazin-1-yl)phenyl]-2'-methyl-4'-(5-methyl-1,2,4- oxadiazol-3-yl) -biphenyl-4-carboxamide], which did not significantly modify serotonin levels alone, abolished this action of GR 46611. Levels of dopamine a nd noradrenaline were not affected by GR 46611 or GR 127,935. In concl usion, there is a complex pattern of reciprocal autoreceptor and heter oceptor control of monoamine release in the frontal cortex. Most notab ly, activation of alpha(2)-adrenergic receptors inhibits the release o f noradrenaline, dopamine and serotonin in each case, while stimulatio n of serotonin-1A receptors suppresses serotonin, yet facilitates nora drenaline and dopamine release. In addition, dopamine D-2/D-3 autorece ptors restrain dopamine release while (terminal-localized) serotonin-1 B receptors reduce serotonin release. Control of serotonin release is expressed phasically and that of noradrenaline and dopamine release to nically. (C) 1998 IBRO. Published by Elsevier Science Ltd.