Dopaminergic control of 125I-labeled neurotensin binding site density in corticolimbic structures of the rat brain.

Abstract

In the rat brain, destruction of dopaminergic cell groups by injections of 6-hydroxydopamine into the ventral mesencephalic tegmentum results in large decreases in the number of neurotensin binding sites in the mesencephalon and the striatum. In contrast, these lesions produce an increase in the number of 1251-labeled neurotensin binding sites in the lateral part of the prefrontal cortex despite a large decrease in cortical dopamine levels. Increases; in the number of 125I-labeled neurotensin binding sites in this cortical area as well as in the entorhinal cortex, the nucleus accumbens, and the central part of the striatum were also obtained after chronic blockade of dopamine neurotransmission by a long-acting neuroleptic pipotiazine palmitic ester. We propose that dopamine inputs regulate the density of postsynaptic neurotensin binding sites through cortical and subcortical dopamine receptors. Therefore, some of the clinical effects of neuroleptics in schizophrenic patients could be partly related to changes in neurotensin neurotransmission.Neurotensin (NT) is a tridecapeptide that is unevenly distributed in mammalian brain (1-4). High levels of NT immunoreactivity have been found in some structures innervated by ascending dopaminergic neurons, such as the nucleus accumbens or the striatum, while relatively little NT immunoreactivity was detected in others, such as the prefrontal cortex (5, 6). Histochemical studies have also revealed the occurrence of NT immunoreactive fibers in the ventral mesencephalic tegmentum (VMT) and in the zona compacta and pars lateralis of the substantia nigra (SN) surrounding dopamine-containing cell bodies and their dendrites (7). In addition, numerous neuronal perikarya of the VMT contain NT immunoreactivity: NT and dopamine coexist in some VMT neurons (7) and the existence of a VMT NT projection to the median nucleus accumbens has been also described (8).There is some indication that NT stimulates the firing rate of nigral dopaminergic cells (9), and several biochemical and behavioral studies have suggested that intraventricularly or locally injected NT can activate dopaminergic cells located either in the VMT or in the SN (10-14). For example, in the rat, the injection of NT into the VMT produced concomitant increases in the levels of dihydroxyphenylacetic acid in the nucleus accumbens and in locomotor activity (13 Although interactions between NT and dopaminergic neurons are well-documented, there is no report about the influence of dopamine neurotransmission on the NT binding sites located post-synaptically to the dopaminergic neurons. In the present study, two approaches were used to chronically interrupt dopamine transmission: the first consisted of the destruction of ascending dopaminergic neurons by bilateral injections of 6-hydroxydopamine into the VMT, and the second took advantage of the property of a long-acting neuroleptic, the pipotiazine palmitic ester, to chronically block dopamine receptors. Changes in NT binding sites were examined by using in vitro qua...

Biochemical and pharmacological profile of a potent and selective nonpeptide antagonist of the neurotensin receptor.

“…Finally, SR 48692 was even more potent than unlabeled neurotensin in binding to guinea pig brain tissues as shown by both radioreceptor assay and autoradiographic techniques. Consistent with the existence of neurotensin binding sites on terminals of the nigrostriatal dopaminergic pathway (29,30), neurotensin was shown to promote an increase in K+-evoked release of [3H]dopamine from rat, cat, and rabbit striatal slices (31)(32)(33). This observation was extended here to guinea pig striatal slices.…”

Electrophysiological Effects of Neurotensin on Globus Pallidus Neurons of 6-Hydroxydopamine-Lesioned Rats

“…For example, unilateral striatal lesions which destroyed a certain proportion of dopaminergic terminals in the lesioned striatum led to slight, but significant, increase of neurotensin-binding site densities in the contralateral striatum [35] . Furthermore, in bilateral 6-OHDA-lesioned rats, the number of neurotensin-binding sites was increased in the lateral part of the prefrontal cortex [36] . However, Masuo et al [37] reported that there was no significant change of neurotensin receptors in the contralateral striatum and substantia nigra of 6-OHDA-lesioned rats, although the expression on contralateral striatum and substantia nigra was much higher than that on the lesioned side.…”

Chronic, but not acute, dosing of antipsychotic drugs alters neurotensin binding in rat brain regions

“…Lesioning studies in the striatum with 6-hydroxy dopamine have demonstrated that there is a close link between dopamine and NT receptor function (Fuxe et al, 1986), whereby striatal lesions produced similar alterations in NT receptor function to administration of chronic haloperidol in the present study. Herve et al (1986) have demonstrated previously that destruction of dopamine cell groups using 6-hydroxydopamine lesions results in decreased numbers of NT binding sites in the striatum and mesencephalon. Furthermore, when the long-acting neuroleptic, pipotiazine palmitic ester was used to produce chronic blockade of dopamine neurotransmission, there was a resulting increase in the density of postsynaptic NT binding sites in the straitum (Herve et al, 1986).…”

“…Herve et al (1986) have demonstrated previously that destruction of dopamine cell groups using 6-hydroxydopamine lesions results in decreased numbers of NT binding sites in the striatum and mesencephalon. Furthermore, when the long-acting neuroleptic, pipotiazine palmitic ester was used to produce chronic blockade of dopamine neurotransmission, there was a resulting increase in the density of postsynaptic NT binding sites in the straitum (Herve et al, 1986). This suggests that there is a close relationship between dopamine and NT systems in the rat brain.…”