Down-regulation of neurotensin receptors after ligand-induced internalization in rat primary cultured neurons

Hermans, Emmanuel; Vanisberg, Marie-Agnès; Geurts, Muriel; Maloteaux, Jean‐Marie

doi:10.1016/s0197-0186(96)00155-6

Cited by 19 publications

(3 citation statements)

References 26 publications

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“…Further investigations are required to determine the mechanisms underlying the difference in effects from 7 and 21-day NT infusion, but it is likely that tolerance to the attenuating effect of acute NT by 7-day infusion is because of down regulation of the NT receptor (Hermans, et al, 1997;Donatodi Paola, et al, 1993), which when prolonged to 21 days, results in compensatory mechanisms possibly involving sensitisation to amphetamine-like dopaminergic activity. Although it is possible that instability of the NT compound in the mini-pumps over 21 days may account for the difference in results, this is unlikely because if NT activity had reduced during the 21-day administration then one would expect no effect on rather than potentiation of AH.…”

Section: Discussionmentioning

confidence: 99%

Effects of chronic infusion of neurotensin and a neurotensin NT1 selective analogue PD149163 on amphetamine-induced hyperlocomotion

et al. 2008

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Neurotensin (NT) has been proposed as an endogenous antipsychotic based in part on the similarity in behavioural effects to antipsychotic drugs, for example, attenuation of both amphetamine-induced hyperlocomotion (AH) and amphetamine disrupted pre-pulse inhibition in the rat. However, there is some evidence that repeated administration of NT or an analogue produces behavioural tolerance to such effects. The present experiments sought to confirm and extend these findings by testing the effects on AH of 7 days central administration of NT and the NT1 selective analogue PD 149163 and the effects of 21 days central administration of NT. NT and PD149163 continuously administered for 7 days produced no effect on AH (in contrast to attenuation with a single injection here and previously reported), whereas 21 days of NT administration potentiated AH. Together, these studies report that the effects of NT or a NT analogue on AH depends on the duration of administration of peptide. The results are discussed in comparison with the reported antipsychotic properties of acute administration of NT and possible mechanisms involving NT1 receptors.

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Section: Discussionmentioning

confidence: 99%

Effects of chronic infusion of neurotensin and a neurotensin NT1 selective analogue PD149163 on amphetamine-induced hyperlocomotion

et al. 2008

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“…As predicted from current models, receptor and ligand molecules were co-localized within the same compartments at short time intervals (0-20 min; Figure 9) but were totally dissociated at longer time points (>20 min). As current biochemical data suggest that the NT receptor is not recycled (38,39), it is likely that the dissociated receptor is being targeted to lysosomes for intracellular degradation.…”

Section: Identification Of Endocytic Compartmentsmentioning

confidence: 99%

Fluorescent ligands for studying neuropeptide receptors by confocal microscopy

Beaudet

Nouel

Stroh

et al. 1998

Braz J Med Biol Res

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This paper reviews the use of confocal microscopy as it pertains to the identification of G-protein coupled receptors and the study of their dynamic properties in cell cultures and in mammalian brain following their tagging with specific fluorescent ligands. Principles that should guide the choice of suitable ligands and fluorophores are discussed. Examples are provided from the work carried out in the authors laboratory using custom synthetized fluoresceinylated or BODIPYtagged bioactive peptides. The results show that confocal microscopic detection of specifically bound fluorescent ligands permits high resolution appraisal of neuropeptide receptor distribution both in cell culture and in brain sections. Within the framework of time course experiments, it also allows for a dynamic assessment of the internalization and subsequent intracellular trafficking of bound fluorescent molecules. Thus, it was found that neurotensin, somatostatin and muand delta-selective opioid peptides are internalized in a receptordependent fashion and according to receptor-specific patterns into their target cells. In the case of neurotensin, this internalization process was found to be clathrin-mediated, to proceed through classical endosomal pathways and, in neurons, to result in a mobilization of newly formed endosomes from neural processes to nerve cell bodies and from the periphery of cell bodies towards the perinuclear zone. These mechanisms are likely to play an important role for ligand inactivation, receptor regulation and perhaps also transmembrane signaling. Correspondence

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“…The mechanism of this phenomenon possibly involves the down-regulation of NTS1 receptors. Cell and tissue culture studies have shown that NT receptor stimulation with agonists causes receptor desensitization and internalization (Hermans et al , 1997; Vanisberg et al , 1991), as well as a decrease in cyclic GMP formation (Gilbert et al , 1988; Hermans et al , 1996), although no studies have looked at the time course of receptor down-regulation in vivo . It is thus possible that a time-dependent delay of onset accompanies the development of this behavioral tolerance.…”

Section: Discussionmentioning

confidence: 99%

Repeated effects of the neurotensin receptor agonist PD149163 in three animal tests of antipsychotic activity: Assessing for tolerance and cross-tolerance to clozapine

Chou

Davis

Jones

et al. 2015

Pharmacology Biochemistry and Behavior

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Neurotensin is an endogenous neuropeptide closely associated with the mesolimbic dopaminergic system and shown to possess antipsychotic-like effects. In particular, acute neurotensin receptor activation can inhibit conditioned avoidance response (CAR), attenuate phencyclidine (PCP)-induced prepulse inhibition (PPI) disruptions, and reverse PCP-induced hyperlocomotion. However, few studies have examined the long term effects of repeated neurotensin receptor activation and results are inconsistent. Since clinical administration of antipsychotic therapy often requires a prolonged treatment schedule, here we assessed the effects of repeated activation of neurotensin receptors using an NTS1 receptor selective agonist, PD149163, in 3 behavioral tests of antipsychotic activity. We also investigated whether reactivity to the atypical antipsychotic clozapine was altered following prior PD149163 treatment. Using both normal and prenatally immune activated rats generated through maternal immune activation with polyinosinic:polycytidilic acid, we tested PD149163 in CAR, PCP (1.5 mg/kg)-induced PPI disruption, and PCP (3.2 mg/kg)-induced hyperlocomotion. For each paradigm, rats were first repeatedly tested with vehicle or PD149163 (1.0, 4.0, 8.0 mg/kg, sc) along with vehicle or PCP for PPI and hyperlocomotion tests, then challenged with PD149163 after 2 drug-free days. All rats were then challenged with clozapine (5.0 mg/kg, sc). During the repeated test period, PD149163 exhibited antipsychotic-like effects in all three models. On the PD149163 challenge day, prior drug treatment only caused a tolerance effect in CAR. This tolerance in CAR was transferrable to clozapine, as it enhanced clozapine tolerance in the same group of animals. Although no tolerance effect was seen in the PD149163 challenge for the PCP-induced hyperlocomotion test, the clozapine challenge showed increased sensitivity in groups previously exposed to repeated PD149163 treatment. Our findings suggest repeated exposure to NTS1 receptor agonists can induce a dose-dependent tolerance and cross-tolerance to clozapine to some of its behavioral effects but not others.

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Down-regulation of neurotensin receptors after ligand-induced internalization in rat primary cultured neurons

Cited by 19 publications

References 26 publications

Effects of chronic infusion of neurotensin and a neurotensin NT1 selective analogue PD149163 on amphetamine-induced hyperlocomotion

Effects of chronic infusion of neurotensin and a neurotensin NT1 selective analogue PD149163 on amphetamine-induced hyperlocomotion

Fluorescent ligands for studying neuropeptide receptors by confocal microscopy

Repeated effects of the neurotensin receptor agonist PD149163 in three animal tests of antipsychotic activity: Assessing for tolerance and cross-tolerance to clozapine

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