Skip to main content
Log in

Metabotropic glutamate receptor antagonists but not NMDA antagonists affect conditioned taste aversion acquisition in the parabrachial nucleus of rats

  • Research Article
  • Published:
Experimental Brain Research Aims and scope Submit manuscript

Abstract

The effect of glutamate receptor antagonists on conditioned taste aversion (CTA) was studied in rats. The association of the short-term memory of a gustatory conditioned stimulus (CS) with visceral malaise (unconditioned stimulus, US) in the CTA paradigm takes place in the parabrachial nuclei (PBN) of the brainstem. The first direct evidence of participation of glutamatergic neurotransmission in the PBN during CTA demonstrated that the extracellular level of glutamate rises during saccharin drinking (Bielavska et al. in Brain Res 887:413–417, 2000). Our results show an effect of microdialysis administration of selective GluR antagonists into the PBN on the formation of CTA engram. We used four glutamate receptor (GluR) antagonists of different types (D-AP5, MK-801 as antagonists of ionotropic GluR and L-AP3, MSPG as antagonists of metabotropic GluR). The disruptive effect of MK-801 on CTA formation in the PBN is concentration-dependent, with the greatest inhibition under the higher concentrations eliciting significant disruption. The application of D-AP5 (0.1, 1, 5 mM) did not elicit a statistically significant blockade of CTA acquisition. This indicates that the association of the US–CS in the PBN is not dependent on NMDA receptors. On the contrary, application of L-AP3 (0.1, 1, 5 mM) blocked the CS–US association.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Aguado L, delValle R, Perez L (1997) The NMDA-receptor antagonist ketamine as an unconditioned stimulus in taste aversion learning. Neurobiol Learn Mem 68:189–196

    Article  PubMed  CAS  Google Scholar 

  • Bahar A, Dorfman N, Dudai Y (2004) Amygdalar circuits required for either consolidation or extinction of taste aversion memory are not required for reconsolidation. Eur J Neurosci 19:1115–1118

    Article  PubMed  Google Scholar 

  • Behnisch T, Reymann KG (1993) Coactivation of metabotropic glutamate and N-methyl-d-aspartate receptors is involved in mechanisms of long-term potentiation maintenance in rat hippocampal Ca1 neurons. Neuroscience 54:37–47

    Article  PubMed  CAS  Google Scholar 

  • Berman DE, Hazvi S, Neduva V, Dudai Y (2000) The role of identified neurotransmitter systems in the response of insular cortex to unfamiliar taste: activation of ERK1–2 and formation of a memory trace. J Neurosci 20:7017–7023

    PubMed  CAS  Google Scholar 

  • Bermudez-Rattoni F (2004) Molecular mechanisms of taste-recognition memory. Nat Rev Neurosci 5:209–217

    Article  PubMed  CAS  Google Scholar 

  • Bielavska E, Bures J (1994) Universality of parabrachial mediation of conditioned taste-aversion. Behav Brain Res 60:35–42

    Article  PubMed  CAS  Google Scholar 

  • Bielavska E, Krivanek J (1994) Intracerebral injection of polymyxin-B blocks the acquisition of conditioned taste-aversion in rats. Neurosci Lett 182:239–242

    Article  PubMed  CAS  Google Scholar 

  • Bielavska E, Miksik I, Krivanek J (2000) Glutamate in the parabrachial nucleus of rats during conditioned taste aversion. Brain Res 887:413–417

    Article  PubMed  CAS  Google Scholar 

  • Bills C, Schachtman TR, Serfozo P, Spooren WPJM, Gasparini F, Simonyi A (2005) Effects of metabotropic glutamate receptor 5 on latent inhibition in conditioned taste aversion. Behav Brain Res 157:71–78

    Article  PubMed  CAS  Google Scholar 

  • Bures J, Bermúdez-Rattoni F, Yamamoto T (1998) Conditioned taste aversion. Memory of a special kind. Oxford University Press, Oxford

    Google Scholar 

  • Castroalamancos MA, Donoghue JP, Connors BW (1995) Different forms of synaptic plasticity in somatosensory and motor areas of the neocortex. J Neurosci 15:5324–5333

    PubMed  CAS  Google Scholar 

  • Davis S, Butcher SP, Morris RGM (1992) The Nmda receptor antagonist D-2–amino-5-phosphonopentanoate (D-Ap5) impairs spatial-learning and Ltp in vivo at intracerebral concentrations comparable to those that block Ltp in vitro. J Neurosci 12:21–34

    PubMed  CAS  Google Scholar 

  • Escobar ML, Alcocer I, Chao V (1998) The NMDA receptor antagonist CPP impairs conditioned taste aversion and insular cortex long-term potentiation in vivo. Brain Res 812:246–251

    Article  PubMed  CAS  Google Scholar 

  • Erdtsieckernste EBHW, Feenstra MGP, Botterblom MHA, Vanuum HFM, Sluiter AA, Heinsbroek RPW (1995) C-Fos expression in the rat-brain after pharmacological stimulation of the rat mediodorsal thalamus by means of microdialysis. Neuroscience 66:115–131

    Article  PubMed  CAS  Google Scholar 

  • Fanselow MS, Kim JJ (1994) Acquisition of contextual pavlovian fear conditioning is blocked by application of an NMDA receptor antagonist d, l-2-amino-5-phosphonovaleric acid to the basolateral amygdala. Behav Neurosci 108:210–212

    Article  PubMed  CAS  Google Scholar 

  • Ferreira G, Gutierrez R, De la Cruz V, Bermudez-Rattoni F (2002) Differential involvement of cortical muscarinic and NMDA receptors in short- and long-term taste aversion memory. Eur J Neurosci 16:1139–1145

    Article  PubMed  CAS  Google Scholar 

  • Fifkova E, Marsala J (1967) Stereotaxic atlases for the cat, rabbit and rat. In: Bures J, Petran M, Zachar J (eds) Electrophysiological methods in biological research. Academic, New York

  • Guthmann A, Herbert H (1999) Distribution of metabotropic glutamate receptors in the parabrachial and Kolliker-fuse nuclei of the rat. Neuroscience 89:873–881

    Article  PubMed  CAS  Google Scholar 

  • Gutierrez H, Gutierrez R, Ramirez-Trejo L, Silva-Gandarias R, Ormsby CE, Miranda MI, Bermudez-Rattoni F (1999a) Redundant basal forebrain modulation in taste aversion memory formation. J Neurosci 19:7661–7669

    PubMed  CAS  Google Scholar 

  • Gutierrez H, Hernandez-Echeagaray E, Ramirez-Amaya V, Bermudez-Rattoni F (1999b) Blockade of N-methyl-d-aspartate receptors in the insular cortex disrupts taste aversion and spatial memory formation. Neuroscience 89:751–758

    Article  PubMed  CAS  Google Scholar 

  • Gutierrez R, Rodriguez-Ortiz CJ, De la Cruz V, Nunez-Jaramillo L, Bermudez-Rattoni F (2003) Cholinergic dependence of taste memory formation: evidence of two distinct processes. Neurobiol Learn Mem 80:323–331

    Article  PubMed  CAS  Google Scholar 

  • Jackson A, Sanger DJ (1989) Conditioned taste-aversions induced by phencyclidine and other antagonists of N-methyl-d-aspartate. Neuropharmacology 28:459–464

    Article  PubMed  CAS  Google Scholar 

  • Jane DE, Pittaway K, Sunter DC, Thomas NK, Watkins JC (1995) New phenylglycine derivatives with potent and selective antagonist activity at presynaptic glutamate receptors in neonatal rat spinal-cord. Neuropharmacology 34:851–856

    Article  PubMed  CAS  Google Scholar 

  • Katz DB, Simon SA, Nicolelis MAL (2001) Dynamic and multimodal responses of gustatory cortical neurons in awake rats. J Neurosci 21:4478–4489

    PubMed  CAS  Google Scholar 

  • Kim M, McGaugh JL (1992) Effects of intraamygdala injections of Nmda receptor antagonists on acquisition and retention of inhibitory avoidance. Brain Res 585:35–48

    Article  PubMed  CAS  Google Scholar 

  • Kolesarova D, Petrovicky P (1987) Parabrachial nuclear-complex in the rat (nuclei parabrachiales and nucleus Koelliker-fuse)—detailed cytoarchitectonic division and connections compared. J Hirnforsch 28:517–527

    PubMed  CAS  Google Scholar 

  • Krivanek J (1996) Conditioned taste aversion and protein kinase C in the parabrachial nucleus of rats. Neurobiol Learn Mem 65:154–162

    Article  PubMed  CAS  Google Scholar 

  • Land CL, Riccio DC (1997) d-cycloserine, a positive modulator of the NMDA receptor, enhances acquisition of a conditioned taste aversion. Psychobiology 25:210–216

    CAS  Google Scholar 

  • Madison DV, Malenka RC, Nicoll RA (1991) Mechanisms underlying long-term potentiation of synaptic transmission. Annu Rev Neurosci 14:379–397

    Article  PubMed  CAS  Google Scholar 

  • Martin SJ, Grimwood PD, Morris RGM (2000) Synaptic plasticity and memory: an evaluation of the hypothesis. Annu Rev Neurosci 23:649–711

    Article  PubMed  CAS  Google Scholar 

  • Masugi M, Yokoi M, Shigemoto R, Muguruma K, Watanabe Y, Sansig G, van der Putten H, Nakanishi S (1999) Metabotropic glutamate receptor subtype 7 ablation causes deficit in fear response and conditioned taste aversion. J Neurosci 19:955–963

    PubMed  CAS  Google Scholar 

  • Mickley GA, Remmers-Roeber DR, Crouse C, Peluso R (2000) Ketamine blocks a taste recognition memory in fetal rats. Pharmacol Biochem Behav 67:575–581

    Article  PubMed  CAS  Google Scholar 

  • Miranda MI, Ferreira G, Ramirez-Lugo L, Bermudez-Rattoni F (2002) Glutamatergic activity in the amygdala signals visceral input during taste memory formation. Proc Natl Acad Sci USA 99:11417–11422

    Article  PubMed  CAS  Google Scholar 

  • Miranda MI, McGaugh JL (2004) Enhancement of inhibitory avoidance and conditioned taste aversion memory with insular cortex infusions of 8-Br-cAMP: involvement of the basolateral amygdala. Learn Mem 11:312–317

    Article  PubMed  Google Scholar 

  • Miranda MI, Ramirez-Lugo L, Bermudez-Rattoni F (2000) Cortical cholinergic activity is related to the novelty of the stimulus. Brain Res 882:230–235

    Article  PubMed  CAS  Google Scholar 

  • Moron I, Ramirez-Lugo L, Ballesteros MA, Gutierrez R, Miranda MI, Gallo M, Bermudez-Rattoni F (2002) Differential effects of bicuculline and muscimol microinjections into the nucleus basalis magnocellularis in taste and place aversive memory formation. Behav Brain Res 134:425–431

    Article  PubMed  CAS  Google Scholar 

  • Norgren R (1995) Gustatory pathways. In: Paxinos G (ed) The rat nervous system. Academic, San Diego, pp 751–771

    Google Scholar 

  • Pfaffmann C, Frank M, Norgren R (1979) Neural mechanisms and behavioral aspects of taste. Annu Rev Psychol 30:283–325

    Article  PubMed  CAS  Google Scholar 

  • Reilly S (1999) The parabrachial nucleus and conditioned taste aversion. Brain Res Bull 48:239–254

    Article  PubMed  CAS  Google Scholar 

  • Riedel G, Reymann KG (1996) Metabotropic glutamate receptors in hippocampal long-term potentiation and learning and memory. Acta Physiol Scand 157:1–19

    Article  PubMed  CAS  Google Scholar 

  • Rosenblum K, Berman DE, Hazvi S, Lamprecht R, Dudai Y (1997) NMDA receptor and the tyrosine phosphorylation of its 2B subunit in taste learning in the rat insular cortex. J Neurosci 17:5129–5135

    PubMed  CAS  Google Scholar 

  • Sacchetti B, Baldi E, Tassoni G, Bielavska E (2001) CAMKII inhibition in the parabrachial nuclei elicits conditioned taste aversion in rats. Neurobiol Learn Mem 75:253–261

    Article  PubMed  CAS  Google Scholar 

  • Sacchetti B, Bielavska E (1998) Chelerythrine, a specific PKC inhibitor, blocks acquisition but not consolidation and retrieval of conditioned taste aversion in rat. Brain Res 799:84–90

    Article  PubMed  CAS  Google Scholar 

  • Saugstad JA, Segerson TP, Westbrook GL (1995) l-2-amino-3-phosphonopropionic acid competitively antagonizes metabotropic glutamate receptor-1-alpha and receptor-5 in Xenopus Oocytes. Eur J Pharmacol Mol Pharmacol 289:395–397

    Article  CAS  Google Scholar 

  • Shigemoto R, Mizuno N (2000) Handbook of chemical neuroanatomy, vol 18. Elsevier, Amsterdam

  • Spray KJ, Bernstein IL (2004) Afferent and efferent connections of the parvicellular subdivision of iNTS: defining a circuit involved in taste aversion learning. Behav Brain Res 154:85–97

    Article  PubMed  Google Scholar 

  • Tucci S, Rada P, Hernandez L (1998) Role of glutamate in the amygdala and lateral hypothalamus in conditioned taste aversion. Brain Res 813:44–49

    Article  PubMed  CAS  Google Scholar 

  • Welzl H, Alessandri B, Battig K (1990) The formation of a new gustatory memory trace in rats is prevented by the noncompetitive Nmda antagonist ketamine. Psychobiology 18:43–47

    Google Scholar 

  • Yamamoto T, Fujimoto Y (1991) Brain mechanisms of taste-aversion learning in the rat. Brain Res Bull 27:403–406

    Article  PubMed  CAS  Google Scholar 

  • Yamamoto T (1998) Conditioned taste aversion. In: Bures J, Bermúdez-Rattoni F, Yamamoto T (eds) Memory of a special kind. Oxford, New York, pp 92–107

    Google Scholar 

  • Yamamoto T, Fujimoto Y, Shimura T, Sakai N (1995) Conditioned taste-aversion in rats with excitotoxic brain-lesions. Neurosci Res 22:31–49

    Article  PubMed  CAS  Google Scholar 

  • Yasoshima Y, Morimoto T, Yamamoto T (2000) Different disruptive effects on the acquisition and expression of conditioned taste aversion by blockades of amygdalar ionotropic and metabotropic glutamatergic receptor subtypes in rats. Brain Res 869:15–24

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank J. Bures and A. Stuchlik for their advice and critical comments. We are also grateful to C. Dockery and P. Shafafi for language check. This study was supported by grant MEYS CR, project 1M0002375201, and grant AVOZ5011922 from Academy of Sciences of the Czech Republic.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Karel Vales.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vales, K., Zach, P. & Bielavska, E. Metabotropic glutamate receptor antagonists but not NMDA antagonists affect conditioned taste aversion acquisition in the parabrachial nucleus of rats. Exp Brain Res 169, 50–57 (2006). https://doi.org/10.1007/s00221-005-0127-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00221-005-0127-6

Keywords

Navigation