Galanin and NPY, two peptides with multiple putative roles in the nervous system

The present brief overview we summarize results from several studies focusi ng on two neuropeptides, galanin and neuropeptide Y (NPY) in discrete neuro nal systems, where they coexist with classic transmitters. On the basis of studies in different animal models we propose that these peptides may be in volved in regulation of certain CNS functions and that drugs acting on thei r receptors may be of use in new therapeutic strategies. At the spinel leve l galanin and NPY are regulated in DRG neurons by nerve injury and in dorsa l horn neurons by inflammation. It is possible that this leads to attenuati on of pain sensitivity. Moreover, both peptides may exert trophic effects, for example to enhance regeneration. In the hypothalamic arcuate nucleus NP Y and its receptors are part of the feeding circuitry, and we suggest that derangement of these NPY neurons may at least in part underlay the lethal p henotype of anorectic mice, which die 22 days postnatally after showing dec reased food intake and growth retardation. Expression of NPY and NPY recept ors is changed in the hippocampus of mice comparatively early after prion i noculation, indicating that this peptide system is affected in this spongif orm degenerative disease in a region of importance for learning and memory. Finally, galanin is co-localized with classic monoamine transmitters in tw o central systems, the dorsal raphe serotonin neurons and the locus coerule us noradrenergic neurons. In both cases galanin causes hyperpolarization (a t high concentrations) and prolongs monoamine-induced outward currents (at low concentrations), thus modulating activity in two systems of importance for many brain functions including mood regulation. It may therefore be int eresting to analyse to what extent drugs affecting galaninergic transmissio n also may be efficient in the treatment of, for example, depression.