Inhibitory GABAergic influence on striatal serotonergic transmission exerted in the dorsal raphe as revealed by in vivo voltammetry.

In vivo differential pulse voltammetry with electrochemically treated carbon fiber microelectrodes has been used to investigate the anatomical nature of the GABAergic influence on striatal serotonergic transmission in the rat. Lesion studies and pharmacological treatments demonstrated that the electrochemical signal recorded at 300 mV in the striatum probably corresponds to the oxidation of extracellularly released 5-hydroxyindoleacetic acid. Thus, dorsal raphé lesions or systemic administration of alpha-propyldopacetamide, NSD 1015, pargyline and MK212 decreased, whereas reserpine injection increased the amplitude of the signal. Moreover, L-5-hydroxytryptophan administration caused an increase in the signal which was almost completely prevented by pargyline pretreatment. Acute administration of dipropylacetamide (150 mg/kg i.p.) reduced the amplitude of the signal from the striatum, while injection of gamma-acetylenic GABA (200 mg/kg i.p.) was without effect. Repeated (but not acute) treatment with the GABA receptor agonist, progabide (400 mg/kg i.p.b.i.d. for 14 days), led to a pronounced decrease in the amplitude of the signal from the striatum. A similar effect was observed after intradorsal raphé infusion of GABA (10 and 100 micrograms), gamma-vinyl GABA (100 micrograms) and SL 75102 (10 micrograms), a principal metabolite of progabide. In contrast, local injection of the GABA receptor antagonists, bicuculline (1 and 10 micrograms) or R5135 (0.05 microgram), failed to affect the peak amplitude in the striatum. When infused into the dorsal raphé, R5135 (0.05-0.1 microgram) antagonized the diminution of the signal induced by intradorsal raphé infusion of GABA (100 micrograms) or SL 75102 (10 micrograms). Finally, electrolytic lesion of the habenular nuclei completely blocked the diminution of the signal from striatum induced by an intradorsal raphé infusion of GABA (100 micrograms). These results indicate that the inhibitory GABAergic control of striatal serotonergic transmission is exerted at the level of the dorsal raphé cells and depends upon the integrity of the habenulo-dorsal pathway.