Suggestive evidence for inhibitory effects of galanin on mesolimbic dopaminergic neurotransmission

The objective was to examine effects of galanin(rat) on forebrain monoamine synthesis and on spontaneous locomotor activity in the rat. The rate of mo noamine synthesis was estimated by measuring the accumulation of L-DOPA and 5-HTP, following inhibition of cerebral aromatic L-amino acid decarboxylas e by means of NSD-1015 (100 mg kg(-1) i.p.), after i.c.v. or intracerebral administration of galanin in adult male Wistar rats. Spontaneous locomotor activity was observed in an automated open-field arena (approximate to 0.5 m(2)). The i.c.v. administration of galanin (0.5-5.0 nmol bilaterally) prod uced a dose-dependent, statistically significant, increase in DOPA accumula tion throughout the neostriatum, and in the olfactory bulb, indicating an i ncrease in the rate of DA synthesis. No increase was observed in brain area s where noradrenaline is the predominant catecholamine, such as the neocort ex or the ventral hippocampus. In addition, there was a tendency for an inc rease in 5-HTP accumulation in the dorso-lateral neostriatum and in the acc umbens. The same i.c.v. administration of galanin produced a dose-dependent , and statistically significant, decrease in spontaneous locomotor activity . The effect on forebrain DA synthesis could also be produced by local bila teral application of galanin (2 X 1 nmol) into the ventral tegmental area, but not the nucleus accumbens (2 X 2 nmol). There were no effects on forebr ain DOPA or 5-HTP accumulation by the local application of galanin into the locus coeruleus, or into the dorsal raphe nucleus. It is concluded that th e neuropeptide galanin modulates forebrain dopaminergic neurotransmission. The effect appears to be mediated at the somato-dendritic level of the meso -neostriatal pathway, and could perhaps be utilized to normalize perturbati ons ascribed to dysfunction in this neuronal pathway, such as schizophrenia . (C) 1999 Elsevier Science B.V. All rights reserved.