Mesolimbic dopamine and cortico-accumbens glutamate afferents as major targets for the regulation of the ventral striato-pallidal GABA pathways by neurotensin peptides.

The tridecapeptide neurotensin (NT) acts in the mammalian brain as a primary neurotransmitter or neuromodulator of classical neurotransmitters. Morphological and functional in vitro and in vivo studies have demonstrated the existence of close interactions between NT and dopamine both in limbic and in striatal brain regions. Additionally, biochemical and neurochemical evidence indicates that in these brain regions NT plays also a crucial role in the regulation of the aminoacidergic signalling. It is suggested that in the nucleus accumbens the regulation of prejunctional dopaminergic transmission induced by NT may be primarily due to indirect mechanism(s) involving mediation via the aminoacidergic neuronal systems with increased glutamate release followed by increased GABA release in the nucleus accumbens rather than a direct action of the peptide on accumbens dopaminergic terminals. The neurochemical profile of action of NT in the control of the pattern of dopamine, glutamate and GABA release in the nucleus accumbens differs to a substantial degree from that shown by the peptide in the dorsal striatum. The neuromodulatory NT mechanisms in the regulation of the ventral striato-pallidal GABA pathways are discussed and their relevance for schizophrenia is underlined.