PubMed1989
The release of previously incorporated [3H]serotonin and its presynaptic modulation were studied in slices of rabbit superior colliculus. Electrical stimulation at frequencies of 0.017-3 Hz greatly increased the outflow of tritiated compounds; this response was almost abolished by tetrodotoxin and in a low calcium medium. Unlabelled serotonin, when added in the presence of nitroquipazine, an inhibitor of high-affinity neuronal serotonin uptake, reduced the electrically evoked overflow of tritium, an effect antagonized by metitepin. Given alone, metitepin caused an increase. The evoked overflow was also decreased by clonidine, and the effect of clonidine was counteracted by phentolamine. Phentolamine itself increased the overflow response. However, this was probably not due to antagonism against an inhibitory effect of endogenous noradrenaline because, first, the selective alpha 2-adrenoceptor antagonist idazoxan did not share with phentolamine the overflow-enhancing effect, second, phentolamine continued to increase the overflow after noradrenergic axons had been destroyed by 6-hydroxydopamine, and third, the facilitatory effects of metitepin and phentolamine were not additive. Phentolamine, like metitepin, antagonized the presynaptic inhibitory effect of serotonin, indicating that it may increase the evoked overflow of tritium by blocking serotonin receptors rather than alpha-adrenoceptors. Ethylketocyclazocine decrease the electrically evoked overflow, and its effect was prevented by naloxone: peptides selective for opioid mu- or delta-receptors caused no change. Nicotine increased the basal outflow of tritium (in the absence of electrical stimulation); the increase was attenuated by hexamethonium and low calcium medium. No or minimal changes in tritium outflow were obtained with beta-adrenoceptor, dopamine receptor, muscarine receptor and GABA receptor ligands or with substance P and glutamate. In conjunction with our previous studies, these results indicate that serotonin is a neurotransmitter in the superior colliculus. Its release is modulated through presynaptic autoreceptors (probably 5-HT1), alpha 2-adrenoceptors, opioid kappa-receptors and nicotine receptors, of which only the autoreceptors receive an endogenous input, at least under the experimental conditions chosen. Each of the three groups of collicular monoamine axons that we have studied recently (cholinergic, noradrenergic, serotoninergic) possesses a specific pattern of presynaptic, release-modulating receptors. A physiological role seems likely only for the alpha 2-autoreceptors at the noradrenergic and the 5-HT1-autoreceptors at the serotoninergic axons.