Neurons of origin of the neurotensinergic plexus enmeshing the ventral tegmental area in rat: Retrograde labeling and in situ hybridization combined

The morphological and physiological substrates that underlie the mutual reg ulatory interactions of neurotensin and dopamine in the rat mesotelencephal ic projections and related structures remain to be fully described. A salie nt candidate for neurotensinergic effects on the mesotelencephalic dopamine projection is the dense plexus of neurotensin immunoreactive axons that en meshes the ventral tegmental area and substantia nigra, but the locations o f the neurons that give rise to this plexus have not been identified and it s systemic context remains obscure. To address this, Fluoro-Gold and the ch olera toxin beta subunit, retrogradely transported axonal tracers, were inj ected into the ventral tegmental area of rats and the brains were processed to demonstrate neurons that contained both retrorade tracer immunoreactivi ty and a probe against neurotensin/neuromedin N messenger RNA. Substantial numbers of double-labeled neurons were observed in the rostral part of the lateral septum. and in a region centered on the shared boundaries of the be d nucleus of stria terminalis. ventromedial ventral pallidum. diagonal band of Broca, lateral preoptic area and rostral lateral hypothalamus. A few do uble-labeled neurons were also observed in the dorsal raphe nucleus and adj acent periaqueductal gray. Despite the administration of haloperidol and D- amphetamine to elicit and enhance neurorensin/neuromedin N messenger RNA ex pression in striatum. including the nucleus accumbens and olfactory tubercl e. no double-labeled neurons were observed there. These results identify a novel brain substrate for control of midbrain dopa mine levels. which affect reward mechanisms and motivation. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.