ALPHA-2-ADRENOCEPTOR MODULATION OF RAT VENTRAL HIPPOCAMPAL 5-HYDROXYTRYPTAMINE RELEASE INVIVO

The putative existence of a functional alpha(2)-adrenoceptor-mediated modulation of 5-HT release in vivo from serotonergic neuronal terminals in the ventral hippocampus was investigated using intracerebral microdialysis in chloral hydrate-anaesthetised rats. The alpha(2)-adrenoceptor agonist clonidine (0.01-0.3 mg/kg, SC) dose-dependently decreased the 5-HT output. The response to clonidine was antagonized by systemic or local administration of the alpha(2)-adrenoceptor antagonist idazoxan (0.1 mg/kg, SC, or 10-mu-mol/l, via the dialysis perfusion medium). Similarly, the 5-HT release-suppressing response to the thiazole alpha(2)-adrenoceptor agonist jingsongling (0.1 mg/kg, SC) was blocked by idazoxan (0.1 mg/kg, SC). The mixed beta-adrenoceptor/5-HT1 receptor antagonist pindolol (8.0 mg/kg, SC) did not affect the clonidine-induced reduction of 5-HT release. Tyrosine hydroxylase inhibition by means of alpha-methyl-para-tyrosine (alpha-MT; 250 mg/kg, IP) caused a drastic reduction (> 80%) in dialysate 3,4-dihydroxyphenyl acetic acid (DOPAC) output but did not affect the 5-HT output per se over 3 h post-injection. Nor did the alpha-MT pretreatment prevent, but instead significantly enhanced, the 5-HT release-suppressing effect of clonidine. The results demonstrate that the release of 5-HT from serotonergic nerve terminals in rat ventral hippocampus in vivo is modulated by alpha(2)-adrenoceptors, probably both by heteroreceptors on the axon terminals of the serotonergic neurones and by other alpha(2)-adrenoceptor sites situated pre- and/or postsynaptic to the noradrenergic terminals. Our results also suggest that while functionally operative, these sites may receive little physiological tone, at least in chloral hydrate-anaesthetised rats.