Tonic nicotinic modulation of serotoninergic transmission in the spinal cord

The spinal serotoninergic projection from the raphe magnus has been shown t o modulate nociceptive inputs, and activation of this projection mediates n icotine-elicited analgesia. Here, we investigate the interactions between c holinergic and serotoninergic systems in the spinal cord, by conducting ser otonin [5-hydroxytryptamine (5-HT)] efflux experiments on mouse spinal slic es. At least three spinal populations of nicotinic receptors are distinguis hed that affect 5-HT release. The first could be directly located on seroto ninergic terminals, is insensitive to nanomolar concentrations of methyllic aconitine (MLA), and may be subjected to a basal (not maximal) cholinergic tone. The second is tonically and maximally activated by endogenous acetylc holine, insensitive to nanomolar concentrations of MLA, and present on inhi bitory neurons. The last is also present on inhibitory neurons but is sensi tive to nanomolar concentrations of MLA and not tonically activated by acet ylcholine. Multiple nicotinic acetylcholine receptor populations thus diffe rentially exert tonic or not tonic control on 5-HT transmission in the spin al cord. These receptors may be major targets for nicotine effects on antin ociception. In addition, the presence of a tonic nicotinic modulation of 5- HT release indicates that endogenous acetylcholine plays a role in the phys iological regulation of descending 5-HT pathways to the spinal cord.