Neurotensin concentrations in rat striatum and nucleus accumbens: Further studies of their regulation

Frey, Peter; Lis, Maddalena; Coward, D. M.

doi:10.1016/0197-0186(88)90145-3

Cited by 40 publications

(11 citation statements)

References 18 publications

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“…Both doses of risperidone decreased NT-LI levels in the occipital cortex. Several studies have demonstrated that neuroleptic drugs increase tissue concentrations of NT in both the striatum and the nucleus accumbens (Eggerman and Zahm 1988;Frey et al 1988;Huang and Hanson 1997;Levant et al 1991;Merchant and Dorsa 1993;Merchant et al 1992Merchant et al , 1994a. On the other hand, the atypical antipsychotic clozapine increases NT concentrations only in the nucleus accumbens (Merchant and Dorsa 1993).…”

Section: Discussionmentioning

confidence: 99%

Effects of Haloperidol and Risperidone on Neurotensin Levels in Brain Regions and Neurotensin Efflux in the Ventral Striatum of the Rat

Gruber

Nomikos

Mathé

2002

Neuropsychopharmacology

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Neurotensin (NT) may play a role in the pathophysiology of schizophrenia and in the mechanism of action of antipsychotic drugs. Here we studied the effects of a 30-day regimen of haloperidol (1.15 mg/100 g food) and risperidone (1.15 and 2.3 mg/100 g food) on NT-like immunoreactivity (-LI) levels in brain tissue and NT-LI efflux in the ventral striatum (VSTR) of the rat. Haloperidol, but not risperidone, increased NT-LI levels in the striatum. In the occipital cortex, risperidone, but not haloperidol, decreased levels of NT-LI. In the hippocampus and the frontal cortex both haloperidol and risperidone (the higher dose) increased NT-LI levels. In the VSTR, haloperidol and risperidone (the higher dose) decreased NT-LI efflux and abolished the stimulatory effect of d-amphetamine (1.5 mg/kg, s.c.). Thus, changes in NT occur in response toNeurotensin (NT) is a 13-amino acid peptide originally isolated from hypothalamus (Carraway and Leeman 1973). Several anatomical, behavioral and pharmacological studies have demonstrated an interaction between NT and dopamine (DA) in the central nervous system (CNS). For example, high levels of NT and its binding sites have been found in both the cell body regions, i.e. the substantia nigra pars compacta (SN) and the ventral tegmental area (VTA), as well as the major projection areas of the ascending dopaminergic pathways, i.e. the striatum and the nucleus accumbens (Kasckow and Nemeroff 1991;Lambert et al. 1995; Quirion 1983). Within both the VTA and the SN, NT immunoreactive fibers are found in close proximity to DA cell bodies (Hökfelt et al. 1984); within the VTA, NT is colocalized with DA (Hökfelt et al. 1984;Kalivas 1993), while in the striatal complex, the majority of the NT binding sites in rat are located on DA terminals (Cadet et al. 1991). There exists substantial pharmacological evidence showing that NT is involved in the regulation of DA neurotransmission. For example, local perfusion with NT dose-dependently increases striatal extracellular DA levels without affecting DA metabolite levels and modifies the inhibitory effects of DA-D 1 and DA-D 2 receptor agonists on striatal DA release (Fuxe et al. 1992). In contrast to the striatum, in the nucleus accumbens direct infu- NO . 5 sion of NT does not affect extracellular DA levels, but increases extracellular levels of the DA metabolite homovanillic acid (Chapman et al. 1992). Microinjection of NT into the VTA, produces a dose-dependent in vivo DA release in the nucleus accumbens and also causes a dose-dependent circling behavior (Steinberg et al. 1995). Moreover, blockade of NT receptors by the NT receptor antagonist SR 48692 decreases basal extracellular levels of DA and its metabolites in the nucleus accumbens, suggesting that NT modulates the mesolimbic DA system (Azzi et al. 1998). Neurotensin has also been shown to mimic the effects of neuroleptic drugs in behavioral models of antipsychotic drug action. Thus, centrally injected NT antagonizes psychostimulant-induced locomotor hyperactivity (Ervin et al. 1981;Joli...

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Section: Discussionmentioning

confidence: 99%

Effects of Haloperidol and Risperidone on Neurotensin Levels in Brain Regions and Neurotensin Efflux in the Ventral Striatum of the Rat

Gruber

Nomikos

Mathé

2002

Neuropsychopharmacology

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“…NT levels were examined after cycloheximide-induced inhibition of protein synthesis in order to assess NT synthesis, This method has heen used previously to examine the effects of haloperidol on substance P and NT synthesis (Bannon and Goedert, 1984;Frey et al, 1988). The lack of selectivity of cycloheximide for the synthesis of particular proteins could be potentially confounding if, for example, one neuropeptide modulates the synthesis of another.…”

Section: Discussionmentioning

confidence: 99%

“…NT synthesis was estimated following the method of Frey et al (1988). Briefly, rats were injected with cycloheximide (1 mg/kg, s.c.) followed 60 min later by 0.9% saline or reserpine (5 mg/kg, i.p.).…”

Section: Methodsmentioning

confidence: 99%

“…NT synthesis A modification of the techniques of Frey et al (1988) and Bannon and Goedert (1984) was used to determine whether the reserpine-induced increase in striatal NT levels was attributable to an increase in peptide synthesis. An increase in tissue NT levels was observed following reserpine administration (see Fig.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…Immunohistochemical analysis of striatal NT was carried out following the procedure outlined below, 18-20 hr following the administration of reserpine (5 mg/kg, i.p. ).NT synthesis was estimated following the method of Frey et al (1988). Briefly, rats were injected with cycloheximide (1 mg/kg, s.c.) followed 60 min later by 0.9% saline or reserpine (5 mg/kg, i.p.).…”

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Effects of dopamine depletion on striatal neurotensin: biochemical and immunohistochemical studies

et al. 1989

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Interactions between striatal dopamine (DA) and neurotensin (NT) have been suggested by anatomical, behavioral, and biochemical studies. Nigrostriatal DA neurons, in contrast to mesocotticolimbic DA neurons, do not appear to contain NT. Thus, distinct neuronal elements subserve interactions between DA and NT within the striatum. We have previously demonstrated that reserpine-induced depletion of striatal DA is accompanied by a dose-and time-dependent increase in striatal NT concentrations. In order to further characterize the effects of reserpine and to define the mechanism by which reserpine acts to increase striatal NT concentrations, we have used immunohistochemical and biochemical approaches. lmmunohistochemical examination of rats pretreated with reserpine revealed marked increases in the density of NT-like immunoreactive (NT-Ii) perikarya and fibers, and the development of NT-Ii patches. Pretreatment with reserpine had no apparent effect on NT synthesis, as assessed by examination of cycloheximide-induced inhibition of protein synthesis. However, reserpine administration resulted in a significant decrease in the release of both DA and NT into the striatal extracellular fluid, as measured by in viva microdialysis. These data suggest that the increase in striatal NT concentrations observed after reserpine treatment results from decreased release, rather than increased synthesis of the peptide.Neurotensin (NT) is a tridecapeptide originally isolated from bovine hypothalamus Leeman, 1973,1976) which is heterogeneously distributed through the CNS (Carraway and Leeman, 1976;Uhl et al., 1977;Jennes et al., 1982;Uhl, 1982). The demonstration that NT perikarya, fibers, and receptors exist within the striatum (Young and Kuhar, 198 1;Jennes et al., 1982;Uhl et al., 1982), a brain region known to contain high concentrations of dopamine (DA), has led to studies aimed at elucidating the possible interactions between these transmitters/ modulators in this brain region. Nigrostriatal DA system function is influenced by NT. For example, NT enhances both basal Received Feb. 10, 1989; revised Apr. 27, 1989; accepted June 1, 1989. This and stimulated DA release from striatal slices; these effects may be mediated by NT receptors localized to the terminals of dopaminergic axons (De Quidt and Emson, 1983;Quirion et al., 1985;Hetier et al., 1988). Striatal NT levels have been shown to be influenced by DA; dopamine receptor antagonists have been reported to alter striatal NT levels and distribution (Govoni et al., 1980;Goedert et al., 1985;Frey et al., 1986;Nemeroff, 1986;Letter et al., 1987; Eggerman and Zahm, 1988). We have recently demonstrated that reserpine, which depletes monoamines by disrupting their vesicular storage, produces a dose-and time-related increase in striatal NT concentrations (Bean et al., 1989). The influence of reserpine on striatal NT levels might be anticipated on the basis of a postulated tonic inhibitory influence of DA on striatal NT levels (Merchant et al., 1988a). The increase in striatal NT tiss...

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Distinct and interactive effects of d-amphetamine and haloperidol on levels of neurotensin and its mRNA in subterritories in the dorsal and ventral striatum of the rat

et al. 1998

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Striatal tissue concentrations of neurotensin, expression of neurotensin/neuromedin N (NT/N) mRNA, and numbers of neurotensin-immunoreactive neurons are increased by d-amphetamine (amph), which stimulates dopamine release in the striatum, and haloperidol (hal), a dopamine receptor antagonist with high affinity for D2-like receptors. The possibility that the effects of these drugs involve distinct subpopulations of striatal neurons was addressed in this study, in which the relative numbers and distributions of striatal neuron profiles containing neurotensin immunoreactivity and/or NT/N mRNA were compared following administrations of hal, amph, hal and amph co-administered, and vehicle. Fourteen striatal subterritories in caudate-putamen, nucleus accumbens, and olfactory tubercle were evaluated. Amph produced increases in the expression of neurotensin preferentially in the ventromedial and caudodorsal subterritories of the caudate-putamen, the rostrobasal cell cluster and lateral shell of the nucleus accumbens, and the olfactory tubercle. Haloperidol produced increased neurotensin expression in much of dorsal and ventral striatum, most prominently in the rostral, dorsomedial and ventrolateral quadrants of the caudate-putamen, and in the rostrobasal cell cluster, rostral pole, medial and lateral shell of the nucleus accumbens and the olfactory tubercle. The numbers of neurons responding to amph and hal in all subterritories following co-administration of the two drugs were significantly less than the summed numbers responding individually to amph and hal. Furthermore, in the subterritories where immunohistochemically detectable responses elicited by amph exceeded those produced by hal, co-administration of the two drugs resulted in responses comparable to those elicited by hal given alone. It is suggested that some of the reported anti-dopaminergic behavioral effects of basal ganglia neurotensin may be attenuated in conditions of reduced dopamine neurotransmission.

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Neurotensin concentrations in rat striatum and nucleus accumbens: Further studies of their regulation

Cited by 40 publications

References 18 publications

Effects of Haloperidol and Risperidone on Neurotensin Levels in Brain Regions and Neurotensin Efflux in the Ventral Striatum of the Rat

Effects of Haloperidol and Risperidone on Neurotensin Levels in Brain Regions and Neurotensin Efflux in the Ventral Striatum of the Rat

Effects of dopamine depletion on striatal neurotensin: biochemical and immunohistochemical studies

Distinct and interactive effects of d-amphetamine and haloperidol on levels of neurotensin and its mRNA in subterritories in the dorsal and ventral striatum of the rat

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