The role of neurotensin receptor 1 on fear memory in mice

The role of neurotensin receptor 1 on fear memory in mice

Neurotensin (NT) is commonly found in the central nervous system and the gastrointestinal tract and known to play role as a neurotransmitter/neuromodulator/neurohormone. We aimed to investigate the effect of the neurotensin receptor agonist PD149163 and the neurotensin receptor antagonist SR142948 on contextual and cued fear conditioning. In total 174 male Balb/c mice were divided into 29 groups. In the behavioral experiments, the NT receptor agonist PD149163 (0.25, 1, 4 mg/kg) or NT receptor antagonist SR142948 (0.1, 1, 3 mg/kg) were administered to subjects before conditioning on the first day (acquisition phase) or before the test performed 24 h after conditioning (retrieval). Rota-rod test, contextual and cued fear conditioning test were performed in all groups. It was observed that the neurotensin receptor agonist PD149163 had no effect on learning in the cued fear conditioning test, but enhanced retrieval dose-dependently. The neurotensin receptor antagonist SR142948 did not affect the learning and retrieval processes in cued fear conditioning. In the contextual fear conditioning test, neither the neurotensin receptor agonist PD149163 nor the neurotensin receptor antagonist SR142948 had any effect on the learning or retrieval of fear conditioning. Our results show that neurotensin receptor agonist PD149163 increases amygdala dependent cued fear conditioning responses dose-dependently.

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  • [1] Carraway R, Leeman SE. The isolation of a new hypotensive peptide, neurotensin, from bovine hypothalami. J Biol Chem. 1973; 248 (19): 6854-6861.
  • [2] Carraway R, Leeman SE. Characterization of radioimmunoassayable neurotensin in the rat. Its differential distribution in the central nervous system, small intestine, and stomach. J Biol Chem. 1976; 251 (22): 7045-7052.
  • [3] Boules M, Fredrickson P, Richelson E. Bioactive analogs of neurotensin: focus on CNS effects. Peptides. 2006; 27 (10): 2523-2533.
  • [4] Kleczkowska P, Lipkowski AW. Neurotensin and neurotensin receptors: characteristic, structure-activity relationship and pain modulation--a review. Eur J Pharmacol. 2013; 716 (1-3): 54-60.
  • [5] Ouyang Q, Zhou J, Yang W, Cui H, Xu M, Yi L. Oncogenic role of neurotensin and neurotensin receptors in various cancers. Clin Exp Pharmacol Physiol. 2017; 44(8): 841-846.
  • [6] Bauer EP. Serotonin in fear conditioning processes. Behav Brain Res. 2015; 277: 68-77.
  • [7] Izquierdo I, Furini CR, Myskiw JC. Fear Memory. Physiol Rev. 2016; 96 (2): 695-750.
  • [8] Toth M, Ziegler M, Sun P, Gresack J, Risbrough V. Impaired conditioned fear response and startle reactivity in epinephrine-deficient mice. Behav Pharmacol. 2013; 24 (1): 1-9.
  • [9] Luo Y, Li Z, Tu Q, Xia L. Metoprolol decreases retention of fear memory and facilitates long-term depression in lateral amygdala. Behav Pharmacol. 2020; 31(6): 535-543.
  • [10] Fanselow MS. Contextual fear, gestalt memories, and the hippocampus. Behav Brain Res. 2000; 110 (1-2): 73-81.
  • [11] Kim JJ, Jung MW. Neural circuits and mechanisms involved in Pavlovian fear conditioning: a critical review. Neurosci Biobehav Rev. 2006; 30 (2): 188-202.
  • [12] Lenard L, Laszlo K, Kertes E, Ollmann T, Peczely L, Kovacs A, Kállai V, Zagorácz O, Gálosi R, Karádi Z. Substance P and neurotensin in the limbic system: Their roles in reinforcement and memory consolidation. Neurosci Biobehav Rev. 2018; 85: 1-20.
  • [13] McGaugh JL. Making lasting memories: remembering the significant. Proc Natl Acad Sci U S A. 2013; 110 Suppl 2: 10402-7.
  • [14] McGaugh JL. Consolidating memories. Annu Rev Psychol. 2015; 66: 1-24.
  • [15] Binder EB, Kinkead B, Owens MJ, Nemeroff CB. Neurotensin and dopamine interactions. Pharmacol Rev. 2001; 53 (4): 453-486.
  • [16] Fuxe K, Von Euler G, Agnati LF, Merlo Pich E, O'Connor WT, Tanganelli S, Li XM, Tinner B, Cintra A, Carani C, Benfenati F. Intramembrane interactions between neurotensin receptors and dopamine D2 receptors as a major mechanism for the neuroleptic-like action of neurotensin. Ann N Y Acad Sci.. 1992; 668: 186-204.
  • [17] St-Gelais F, Jomphe C, Trudeau L-E. The role of neurotensin in central nervous system pathophysiology: what is the evidence? J Psychiatry Neurosci. 2006; 31(4): 229-245
  • [18] Vadnie CA, Ayers-Ringler J, Oliveros A, et al. Antipsychotic-like effects of a neurotensin receptor type 1 agonist. Behav Brain Res. 2016; 305: 8-17.
  • [19] Azmi N, Norman C, Spicer CH, Bennett GW. Effects of a neurotensin analogue (PD149163) and antagonist (SR142948A) on the scopolamine-induced deficits in a novel object discrimination task. Behav Pharmacol. 2006; 17 (4): 357-362.
  • [20] Tyler-McMahon BM, Boules M, Richelson E. Neurotensin: peptide for the next millennium. Regul Pept. 2000; 93 (1- 3): 125-136.
  • [21] Ferraro L, Tomasini MC, Mazza R, Fuxe K, Fournier J, Tanganelli S, Antonelli T. Neurotensin receptors as modulators of glutamatergic transmission. Brain Res Rev.. 2008; 58 (2): 365-373.
  • [22] Ollmann T, Péczely L, László K, et al. Anxiolytic effect of neurotensin microinjection into the ventral pallidum. Behav Brain Res. 2015; 294: 208-214.
  • [23] Shilling PD, Feifel D. The neurotensin-1 receptor agonist PD149163 blocks fear-potentiated startle. Pharmacol Biochem Behav. 2008; 90(4): 748-752
  • [24] Prus AJ, Hillhouse TM, LaCrosse AL. Acute, but not repeated, administration of the neurotensin NTS1 receptor agonist PD149163 decreases conditioned footshock-induced ultrasonic vocalizations in rats. Prog Neuropsychopharmacol Biol Psychiatry. 2014; 49: 78-84
  • [25] Tirado-Santiago G, Lazaro-Munoz G, Rodriguez-Gonzalez V, Maldonado-Vlaar CS. Microinfusions of neurotensin antagonist SR 48692 within the nucleus accumbens core impair spatial learning in rats. Behav Neurosciehavioral neuroscience. 2006; 120 (5): 1093-1102.
  • [26] Xiao Z, Cilz NI, Kurada L, Hu B, Yang C, Wada E, Combs CK, Porter JE, Lesage F, Lei S. Activation of neurotensin receptor 1 facilitates neuronal excitability and spatial learning and memory in the entorhinal cortex: beneficial actions in an Alzheimer's disease model. J Neurosci. 2014; 34 (20): 7027-42. in fear memory in mice. J Neurochem. 2007; 102 (5): 1669-1676.
  • [27] Antonelli T, Fuxe K, Tomasini MC, Mazzoni E, Agnati LF, Tanganelli S, Ferraro L. Neurotensin receptor mechanisms and its modulation of glutamate transmission in the brain: relevance for neurodegenerative diseases and their treatment. Prog Neurobiol. 2007; 83 (2): 92-109.
  • [28] Gully D, Canton M, Boigegrain R, Jeanjean F, Molimard JC, Poncelet M, Gueudet C, Heaulme M, Leyris R, Brouard A. Biochemical and pharmacological profile of a potent and selective nonpeptide antagonist of the neurotensin receptor. Proc Natl Acad Sci U S A. 1993; 90 (1): 65-69.
  • [29] Yamauchi R, Wada E, Kamichi S, Yamada D, Maeno H, Delawary M, Nakazawa T, Yamamoto T, Wadaet K. Neurotensin type 2 receptor is involved in fear memory in mice. J Neurochem. 2007; 102 (5): 1669-1676.
  • [30] Laszlo K, Toth K, Kertes E, Peczely L, Ollmann T, Lenard L. Effects of neurotensin in amygdaloid spatial learning mechanisms. Behav Brain Res. 2010; 210 (2): 280-283.
  • [31] Yamada D, Wada E, Amano T, Wada K, Sekiguchi M. Lack of neurotensin type 1 receptor facilitates contextual fear memory depending on the memory strength. Pharmacol Biochem Behav. 2010; 96 (3): 363-369.
  • [32] Toda H, Boku S, Nakagawa S, Inoue T, Kato A, Takamura N, Song N, Nibuya M, Koyama T, Kusumiet I. Maternal separation enhances conditioned fear and decreases the mRNA levels of the neurotensin receptor 1 gene with hypermethylation of this gene in the rat amygdala. PloS one. 2014; 9(5): e97421.
  • [33] Keiser AA, Matazel KS, Esser MK, Feifel D, Prus AJ. Systemic administration of the neurotensin NTS(1)-receptor agonist PD149163 improves performance on a memory task in naturally deficient male brown Norway rats. Exp Clin Psychopharmacol. 2014; 22 (6): 541-547.
Journal of research in pharmacy (online)-Cover
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: Marmara Üniversitesi
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