SR 48692, a non-peptide neurotensin receptor antagonist differentially affects neurotensin-induced behaviour and changes in dopaminergic transmission

Steinberg, R.; Brun, P; Fournier, Marie; Souilhac, J.; Rodier, Daniel; Mons, G.; Terranova, Jean-Paul; Fur, G. Le; Soubrié, Philippe

doi:10.1016/0306-4522(94)90295-x

Cited by 81 publications

(60 citation statements)

References 28 publications

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Section: Discussionmentioning

confidence: 97%

“…Conversely, NT microinjection into the NAC decreases the behavioral responses induced by DA agonists, such as amphetamine, cocaine or apomorphine (Ervin et al 1981; Ford and Marsden 1990;Robledo et al 1993). Both of these NT-induced behavioral effects were reversed by systemic acute injection of SR 48692 (Steinberg et al 1994) suggesting that NT receptors in the VTA and the NAC could be possible brain sites of SR 48692 action.Given the importance of the DA mesolimbic system in the mediation of behavioral sensitization and the numerous interactions between DA and NT systems, we can postulate that the SR 48692 effect shown in our study is related to its ability to affect several aspects of DA neurons functioning. We previously reported that SR 48692 administration for two weeks, at the dose of 1 mg/kg, produced a drastic reduction in the basal extracellular levels of DA in the NAC (Azzi et al 1998).…”

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confidence: 97%

“…1 Neurotensin and Behavioral Responses to Amphetamine 71 1997). These effects of SR 48692 on DA systems were not found after acute administration (Steinberg et al 1994) and appeared only after prolonged treatment (Santucci et al 1997; Azzi et al 1998). Together, these data indicate that SR 48692 per se, when administered chronically, attenuates the DA mesolimbic activity, an effect that may somehow counteract those produced by repeated administration of psychostimulants.…”

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confidence: 98%

“…In vitro binding studies from various species brain tissue revealed that SR 48692 can bind to both NT1 and NT2, but with a much lower affinity for the latter (Gully et al 1993) and displays no affinity for NT3 (Mazella et al 1998). Acute systemic administration of SR 48692 reverses the turning behavior induced by intrastriatal injection of NT in mice (Poncelet et al 1994) and controlateral circling induced by intra-VTA injection of NT in rats (Steinberg et al 1994). However, SR 48692, even over a wide dose range (0.5-4 mg/kg), fails to antagonize NT-induced analgesia in mice and rats, an effect mediated by NT2 receptors (Dubuc et al 1994(Dubuc et al , 1999.…”

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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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Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 97%

mentioning

confidence: 98%

mentioning

confidence: 99%

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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 compound, first identified as a NTS1 antagonist, presented a higher affinity for this receptor than for NTS2, while the analog SR 142948A did not discriminate between these two 5 receptors [25]. Experiments performed with these compounds [25,37,71] as well as intracerebral injection of anti-receptor antisense oligonucleotides [19] or evaluation of knockout mice [59], suggested that most of the NT effects could be attributed to stimulation of NTS1. However, the functional importance of NTS2 and NTS3 might still be largely underestimated.…”

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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Involvement of cortical neurotensin in the regulation of rat meso-cortico-limbic dopamine neurons: Evidence from changes in the number of spontaneously active A10 cells after neurotensin receptor blockade

Santucci

Gueudet

Steinberg

et al. 1997

Synapse

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In order to further assess the role of endogenous neurotensin on midbrain dopaminergic neuronal function, the effects of the selective neurotensin receptor antagonists SR 48692 and SR 48527 were investigated on the number of spontaneously active A9 and A10 dopaminergic neurons in rats. Single intraperitoneal administration of SR 48692 (0.1-3 mg/kg) dose-dependently increased the number of active A10, but not A9 cells. SR 48527 (1 mg/kg) had a similar profile, but not SR 49711, its low affinity R-enantiomer, indicating that the effects observed were mediated through neurotensin receptor blockade. Five-week treatment with SR 48692 (3 mg/kg/day) produced a significant decrease of the number of active A10, but not A9 cells, which was reversed by apomorphine, suggesting that these cells were under depolarization block. Single co-administration of inactive doses of SR 48692 (0.1 mg/kg) and haloperidol (0.0625 mg/kg) significantly increased the number of active A10 cells. Conversely, co-administered active doses of SR 48692 or SR 48527 and haloperidol (1 and 0.25 mg/kg, respectively) induced an apomorphine-sensitive decrease of the number of A10 active cells. Finally, SR 48692 (10 mg/kg) modified neither accumbal nor cortical basal DA release. Local micro-injection of SR 48692 (10[-11]-10[-9] M), but not that of SR 49711 (10[-9] M), into the prefrontal cortex, increased the number of active A10 cells in a concentration-dependent manner. These results suggest that neurotensin receptor blockade counteracts a tonic inhibitory regulation by endogenous neurotensin of mesolimbic dopaminergic function and indicate that the prefrontal cortex is critically involved in this regulation.

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SR 48692, a non-peptide neurotensin receptor antagonist differentially affects neurotensin-induced behaviour and changes in dopaminergic transmission

Cited by 81 publications

References 28 publications

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

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

Interactions between neurotensin receptors and G proteins

Involvement of cortical neurotensin in the regulation of rat meso-cortico-limbic dopamine neurons: Evidence from changes in the number of spontaneously active A10 cells after neurotensin receptor blockade

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