Neurotensin and neurotensin receptors

Vincent, Jean‐Pierre; Mazella, Jean; Kitabgi, Patrick

doi:10.1016/s0165-6147(99)01357-7

Cited by 500 publications

(411 citation statements)

References 61 publications

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“…SR 48692 is a NT receptor antagonist that is relatively selective for NT 1 , the receptor subtype that has so far been implicated in the pre-and postsynaptic effects of NT on the mesolimbic and nigrostriatal dopamine system (Gully et al, 1993;Tyler et al, 1998;Vincent et al, 1999). NT 2 , another Gprotein coupled NT receptor, is also widely expressed in the brain including dopaminergic nuclei (the ventral tegmental area and substantia nigra) and the NAcc and its activation could be involved in APD-induced Fos expression in some brain regions (Walker et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…NT 2 , another Gprotein coupled NT receptor, is also widely expressed in the brain including dopaminergic nuclei (the ventral tegmental area and substantia nigra) and the NAcc and its activation could be involved in APD-induced Fos expression in some brain regions (Walker et al, 1998). SR 142948A has equal affinity for NT 1 and NT 2 in the nanomolar range and several studies indicate that SR 48692 and SR 142948A may also distinguish between different pharmacological NT receptor subtypes (Gully et al, 1997;Vincent et al, 1999). We chose to use SR 142948A, as it cannot be ruled out that effects of NT at NT 2 may also contribute to APD-induced Fos expression.…”

Section: Discussionmentioning

confidence: 99%

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Neurotensin Receptor Antagonist SR 142948A Alters Fos Expression and Extrapyramidal Side Effect Profile of Typical and Atypical Antipsychotic Drugs

Binder

Kinkead

Owens

et al. 2004

Neuropsychopharmacol

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Antipsychotic drugs (APDs) have previously been shown to alter Fos expression in a regionally specific manner. Increases in Fos expression in the nucleus accumbens (NAcc) are common to all clinically effective APDs. In contrast, APD-induced Fos expression increases in the caudate-putamen (CPu) and prefrontal cortex (PFC) are associated with the extrapyramidal side effect liability of typical APDs or the effectiveness against negative symptoms of atypical APDs, respectively. Considerable evidence suggests that the neuropeptide neurotensin (NT) mediates some of the effects of APDs. To determine whether NT neurotransmission is also involved in APD-induced Fos expression in brain regions relevant for therapeutic efficacy, the NT receptor antagonist SR 142948A (10 or 100 mg/ kg i.p.) was coadministered with APDs (haloperidol (2.0 mg/kg s.c.), olanzapine (5 mg/kg i.p.), or clozapine (20 mg/kg s.c.)). Fos expression was evaluated in the PFC, NAcc shell, dorsomedial, and dorsolateral CPu and the lateral septum. SR 142948A attenuated haloperidolinduced Fos expression in the CPu but, in contrast, increased olanzapine-induced Fos expression in this brain region. The effects of the NT receptor antagonist were paralleled by its effects on catalepsy in olanzapineFbut not haloperidolFtreated animals.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Neurotensin Receptor Antagonist SR 142948A Alters Fos Expression and Extrapyramidal Side Effect Profile of Typical and Atypical Antipsychotic Drugs

Binder

Kinkead

Owens

et al. 2004

Neuropsychopharmacol

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“…However, according to the pharmacological properties of NT receptors and their localization in the brain, several potential targets for SR 48692 can be proposed. Two types of functionally relevant NT receptors (for review see Vincent et al 1999) have been identified and cloned from rodent and human brains, and shown to belong to the family of seven transmembrane domains G-protein-coupled receptors (Tanaka et al 1990;Vita et al 1993; Chalon et al 1996;Mazella et al 1996). The subtype 1 (NT1) shows a high affinity for NT (KdӍ0.1-0.3 nM) whereas the subtype 2 (NT2) shows a lower affinity for the peptide (KdӍ2-4 nM) and is sensitive to levocabastine, a histamine antagonist.…”

Section: Discussionmentioning

confidence: 99%

Chronic Blockade of Neurotensin Receptors Strongly Reduces Sensitized, but Not Acute, Behavioral Response to D-amphetamine

Panayi

Dorso

Lambás‐Señas

et al. 2002

Neuropsychopharmacology

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This study investigated the effect of a chronic blockade of neurotensin (NT) receptors on the sensitized behavioral response to amphetamine using a nonpeptide NT receptor antagonist, SR 48692. Rats received four injections of D-amphetamine (0.5 or 1 mg/kg, IP) every other day (day 1, 3, 5 and 7) and were then challenged with the same dose of amphetamine after a 6-day withdrawal (day 14) to establish the presence of locomotor sensitization. Daily administration of SR 48692 (1 mg/kg, IP) throughout the amphetamine regimen (day 1 to day 14) almost completely blocked the sensitized locomotor response to amphetamine without affecting stereotyped behaviors (experiment 1). The decreased amphetamine-induced sensitization in chronically SR 48692-treated rats did not appear to result from an influence on basal locomotor activity, as chronic SR 48692 treatment did not modify the spontaneous locomotor activity developed in response to mild stresses (experiment 2). Moreover, we showed that chronic pretreatment with SR 48692 (1 mg/kg, 14 daily IP injections) had no effect on the locomotor activation induced by a single IP administration of amphetamine (experiment 3). These data suggest that a sustained blockade of NTRepeated intermittent administration of psychostimulants, such as amphetamine and cocaine, leads to a progressive enhancement of their behavioral stimulant effects, as well as a long-lasting hyperreactivity in response to environmental or pharmacological challenges (Antelman et al. 1980;Kalivas and Stewart 1991). This phenomenon, termed behavioral sensitization, is considered as a useful animal model for drug-induced psychosis and drug craving in humans (Robinson and Becker 1986;Robinson and Berridge 1993;Lieberman et al. 1997;Laruelle 2000).The mesoaccumbens dopaminergic (DA) system, which originates within the ventral tegmental area (VTA) and projects to the nucleus accumbens (NAC), plays an important role in the behavioral sensitization to psychostimulants. Thus, repeated injections of am- phetamine into the VTA produce sensitized locomotor responses to systemic injections of amphetamine, cocaine and morphine. In contrast, although amphetamine produces locomotor stimulation upon acute injection into the NAC, repeated intra-NAC injections do not lead to sensitization (Kalivas and Weber 1988;Vezina and Stewart 1990; Hooks et al. 1992; Cador et al. 1995). Other studies have established that the mechanisms leading to the induction of sensitization require the action of DA, somatodendritically released by amphetamine, on D1 receptors in the VTA whereas DA release in the NAC appears as the prime event for the expression of behavioral sensitization (Vezina 1993(Vezina , 1996Pierce and Kalivas 1997a). However, recent studies support the view that the neural underpinnings of behavioral sensitization implicate additional limbic areas and neurotransmitters such as the medial prefrontal cortex (mPFC) and its glutamatergic components (Wolf 1998; Cador et al. 1999) or the ventral pallidum and its GABAergic components (Pier...

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“…Neurotensin (NT), a 13-aminoacid peptide [13], acts as a neuromodulator in the brain and a paracrine or circulating hormone in periphery [38,74]. NT agonists or antagonists have been suggested to be of potential use for the treatment of pain, eating disorders, psychotic troubles, drug abuse and stress [6,36,64,37].…”

Section: Introductionmentioning

confidence: 99%

Interactions between neurotensin receptors and G proteins

Pélaprat

2006

Peptides

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Abstract:Three neurotensin (NT) receptors have been cloned to date, two of which, NTS1 and NTS2, belonging to the family of seven transmembrane domain receptors coupled to G proteins (GPCRs). NTS1 and NTS2 may activate multiple signal transduction pathways, involving several G proteins. However, whereas NT acts as an agonist towards all NTS1-mediated pathways, this peptide exerts agonist or antagonist activities depending on the considered NTS2-mediated pathway. Studies on these receptors reinforce the concept of independence between multiple signals potentially mediated through a single GPCR, generating a wide diversity of functional responses depending on the host cell and the ligand.

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Neurotensin and neurotensin receptors

Cited by 500 publications

References 61 publications

Neurotensin Receptor Antagonist SR 142948A Alters Fos Expression and Extrapyramidal Side Effect Profile of Typical and Atypical Antipsychotic Drugs

Neurotensin Receptor Antagonist SR 142948A Alters Fos Expression and Extrapyramidal Side Effect Profile of Typical and Atypical Antipsychotic Drugs

Chronic Blockade of Neurotensin Receptors Strongly Reduces Sensitized, but Not Acute, Behavioral Response to D-amphetamine

Interactions between neurotensin receptors and G proteins

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