Suggestive evidence for inhibitory effects of galanin on mesolimbic dopaminergic neurotransmission

• Published in: Brain research 1999-03, Vol.822 (1), p.200-209
• Main Authors: Ericson, Evalena, Ahlenius, Sven
• Format: Article
• Language: English
• Subjects: 5-Hydroxytryptophan - metabolism; Animals; Behavior; Behavior, Animal - drug effects; Biological and medical sciences; Bradykinin - analogs & derivatives; Bradykinin - pharmacology; Brain Chemistry - drug effects; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Dopamine; Dopamine - biosynthesis; Dopamine - metabolism; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Galanin - analogs & derivatives; Galanin - pharmacology; Galanin rat; Galantide; Hippocampus - chemistry; Hippocampus - metabolism; Injections, Intraventricular; Levodopa - metabolism; Locomotion - drug effects; Male; Monoamine; Motor Activity - drug effects; Neocortex - chemistry; Neocortex - metabolism; Neostriatum - chemistry; Neostriatum - metabolism; Neural Inhibition - drug effects; Nucleus Accumbens - chemistry; Nucleus Accumbens - metabolism; Olfactory Bulb - chemistry; Olfactory Bulb - metabolism; Peptide Fragments - pharmacology; Rat; Rats; Rats, Wistar; Substance P - analogs & derivatives; Substance P - pharmacology; Synaptic Transmission - drug effects; Synthesis; Ventral Tegmental Area - chemistry; Ventral Tegmental Area - metabolism; Vertebrates: nervous system and sense organs
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(99)01144-0

The objective was to examine effects of galanin rat on forebrain monoamine synthesis and on spontaneous locomotor activity in the rat. The rate of monoamine synthesis was estimated by measuring the accumulation of l-DOPA and 5-HTP, following inhibition of cerebral aromatic l-amino acid decarboxylase 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 (≈0.5 m 2). The i.c.v. administration of galanin (0.5–5.0 nmol bilaterally) produced a dose-dependent, statistically significant, increase in DOPA accumulation throughout the neostriatum, and in the olfactory bulb, indicating an increase in the rate of DA synthesis. No increase was observed in brain areas where noradrenaline is the predominant catecholamine, such as the neocortex or the ventral hippocampus. In addition, there was a tendency for an increase in 5-HTP accumulation in the dorso-lateral neostriatum and in the accumbens. 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 bilateral application of galanin (2×1 nmol) into the ventral tegmental area, but not the nucleus accumbens (2×2 nmol). There were no effects on forebrain 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 the 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 perturbations ascribed to dysfunction in this neuronal pathway, such as schizophrenia.