Share This Article:

Effects of Neurokinin-1 Receptor Inhibition on Anxiety Behavior in Neonatal Rats Selectively Bred for an Infantile Affective Trait

Abstract Full-Text HTML XML Download Download as PDF (Size:1000KB) PP. 859-864
DOI: 10.4236/pp.2014.59096    2,888 Downloads   3,379 Views   Citations

ABSTRACT

Interest in understanding the etiology and developing new treatments for anxiety disorders in children and adolescents has led to recent studies of neurotransmitters not traditionally associated with neural pathways for fear and anxiety. The binding of the neurotransmitter substance P (SP) to its neurokinin-1 (NK1) receptor may be a crucial component in mediating the anxiety response. While previous studies using rodent models have documented the anxiolytic effects of SP antagonists, the role of individual differences in affective temperament has not yet been examined in studies of drug response. This study used intracerebroventricular injections of the NK1 antagonist Spantide II at concentrations of 10 and 100 pmol to examine the consequences of blocking the SP-NK1 pathway in high and low line rats selectively bred for high or low levels of ultrasonic distress calls after a brief maternal separation. Affective temperament was a significant factor in determining drug response. Spantide II resulted in a significant reduction of distress calls in subjects in the high anxiety line, while low line subjects with low anxiety were resistant to the drug. These data indicate that the SP-NK1 pathway could be an important therapeutic target for the treatment of various stress disorders, but drug response might be influenced by the individual’s state anxiety or history of chronic stress.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Schott, A. and Zimmerberg, B. (2014) Effects of Neurokinin-1 Receptor Inhibition on Anxiety Behavior in Neonatal Rats Selectively Bred for an Infantile Affective Trait. Pharmacology & Pharmacy, 5, 859-864. doi: 10.4236/pp.2014.59096.

References

[1] Baxter, A.J., Scott, K.M., Vos, T. and Whiteford, H.A. (2012) Global Prevalence of Anxiety Disorders: A Systematic Review and Meta-Regression. Psychological Medicine, 43, 897-910.
http://dx.doi.org/10.1017/S003329171200147X
[2] Merikangas, K.R., He, J.P., Burstein, M., Swanson, S.A., Avenevoli, S., Cui, L., Benjet, C., Georgiades, K. and Swendsen, J. (2010) Lifetime Prevalence of Mental Disorders in U.S. Adolescents: Results from the National Comorbidity Survey Replication—Adolescent Supplement (NCS-A). Journal of the American Academy of Child and Adolescent Psychiatry, 49, 980-989.
http://dx.doi.org/10.1016/j.jaac.2010.05.017
[3] Salum, G.A., Desousa, D.A., do Rosário, M.C., Pine, D.S. and Manfro, G.G. (2013) Pediatric Anxiety Disorders: From Neuroscience to Evidence-Based Clinical Practice. Revista Brasileira de Psiquiatria, 35, S3-S21.
http://dx.doi.org/10.1590/1516-4446-2013-S108
[4] Ebner, K., Muigg, P., Singewald, G. and Singewald, N. (2008) Substance P in Stress and Anxiety: NK-1 Receptor Antagonism Interacts with Key Brain Areas of the Stress Circuitry. Annals of the New York Academy of Sciences, 1144, 61-73.
http://dx.doi.org/10.1196/annals.1418.018
[5] Ebner, K. and Singewald, N. (2006) The Role of Substance P in Stress and Anxiety Responses. Amino Acids, 31, 251-272.
http://dx.doi.org/10.1007/s00726-006-0335-9
[6] Mantyh, P.W. (2002) Neurobiology of Substance P and the NK1 Receptor. Journal of Clinical Psychiatry, 11, 6-10.
[7] De Araújo, J.E., Silva, R.C., Huston, J.P. and Brandão, M.L. (1999) Anxiogenic Effects of Substance P and Its 7-11 C Terminal, but Not the 1-7 N Terminal, Injected into the Dorsal Periaqueductal Gray. Peptides, 20, 1437-1443.
http://dx.doi.org/10.1016/S0196-9781(99)00154-0
[8] Steimer, T. (2011) Animal Models of Anxiety Disorders in Rats and Mice: Some Conceptual Issues. Dialogues in Clinical Neuroscience, 13, 495-506.
[9] Bilkei-Gorzo, A. and Zimmer, A. (2005) Mutagenesis and Knockout Models: NK1 and Substance P. Handbook of Experimental Pharmacology, 169, 143-162.
http://dx.doi.org/10.1007/3-540-28082-0_5
[10] Kramer M.S., Cutler, N., Feighner, J., Shrivastava, R., Carman, J., Sramek, J.J., et al. (1998) Distinct Mechanism for Antidepressant Activity by Blockade of Central Substance P Receptors. Science, 281, 1640-1645.
http://dx.doi.org/10.1126/science.281.5383.1640
[11] Brenes, J.C., Broiz, A.C., Bassi, G.S., Schwarting, R.K.W. and Brandão, M.L. (2012) Involvement of Midbrain Tectum Neurokinin-Mediated Mechanisms in Fear and Anxiety. Brazilian Journal of Medical and Biological Research, 45, 349-356.
http://dx.doi.org/10.1590/S0100-879X2012007500030
[12] Carvalho, C., Santos, J.M., Bassi, G.S. and Brandão, M.L. (2013) Participation of NK1 Receptors of the Amygdala on the Processing of Different Types of Fear. Neurobiology of Learning and Memory, 102, 20-27.
http://dx.doi.org/10.1016/j.nlm.2013.03.004
[13] Allin, J.T. and Banks, E.M. (1972) Functional Aspects of Ultrasound Production by Infant Albino Rats (Rattus norvegicus). Animal Behavior, 20, 175-185.
http://dx.doi.org/10.1016/S0003-3472(72)80189-1
[14] Carden, S.E. and Hofer, M.A. (1990) Independence of Benzodiazepine and Opiate Action in the Suppression of Isolation Distress in Rat Pups. Behavioral Neuroscience, 104, 160-166.
http://dx.doi.org/10.1037/0735-7044.104.1.160
[15] Winslow, J.T. and Insel, T.R. (1991) The Infant Rat Separation Paradigm: A Novel Test for Novel Anxiolytics. Trends in Pharmacological Sciences, 12, 402-404.
http://dx.doi.org/10.1016/0165-6147(91)90616-Z
[16] Zimmerberg, B., Brunelli, S.A. and Hofer, M.A. (1994) Reduction of Rat Pup Ultrasonic Vocalizations by the Neuroactive Steroid Allopregnanolone. Pharmacology, Biochemistry and Behavior, 47, 735-738.
http://dx.doi.org/10.1016/0091-3057(94)90181-3
[17] Brunelli, S.A. (2005) Development and Evolution of Hidden Regulators: Selective Breeding for an Infantile Phenotype. Developmental Psychobiology, 47, 243-252.
http://dx.doi.org/10.1002/dev.20090
[18] Brunelli, S.A. and Hofer, M.A. (2007) Selective Breeding for Infant Rat Separation-Induced Ultrasonic Vocalizations: Developmental Precursors of Passive and Active Coping Styles. Behavioural Brain Research, 182, 193-207.
http://dx.doi.org/10.1016/j.bbr.2007.04.014
[19] Zimmerberg, B., Brunelli, S.A., Fluty, A.J. and Frye, C.A. (2005) Differences in Affective Behaviors and Hippocampal Allopregnanolone Levels in Adult Rats of Lines Selectively Bred for Infantile Vocalizations. Behavioral Brain Research, 159, 301-311.
http://dx.doi.org/10.1016/j.bbr.2004.11.009
[20] Schwarting, R.K.W. and Wöhr, M. (2012) On the Relationships between Ultrasonic Calling and Anxiety-Related Behavior in Rats. Brazilian Journal of Medical and Biological Research, 45, 337-348.
http://dx.doi.org/10.1590/S0100-879X2012007500038
[21] de Gomes, V., Hassan, W., Maisonnette, S., Johnson, L.R., Ramos, A. and Landeira-Fernandez, J. (2013) Behavioral Evaluation of Eight Rat Lines Selected for High and Low Anxiety-Related Responses. Behavioural Brain Research, 257, 39-48.
http://dx.doi.org/10.1016/j.bbr.2013.09.028
[22] Håkanson, R., Leander, S., Asano, N., Feng, D.M. and Folkers, K. (1990) Spantide II, a Novel Tachykinin Antagonist Having High Potency and Low Histamine-Releasing Effect. Regulatory Peptides, 31, 75-82.
http://dx.doi.org/10.1016/0167-0115(90)90197-5
[23] Glascock, J.J., Osman, E.Y., Coady, T.H., Rose, F.F., Shababi, M. and Lorson, C.L. (2011) Delivery of Therapeutic Agents through Intracerebroventricular (ICV) and Intravenous (IV) Injection in Mice. Journal of Visualized Experiments, 56, 2968.
http://dx.doi.org/10.3791/2968
[24] Liu, H., Mazarati, A.M., Katsumori, H., Sankar, R. and Wasterlain, C.G. (1999) Substance P Is Expressed in Hippocampal Principal Neurons during Status Epilepticus and Plays a Critical Role in the Maintenance of Status Epilepticus. Proceedings of the National Academy of Sciences of the United States of America, 96, 5286-5291.
http://dx.doi.org/10.1073/pnas.96.9.5286
[25] Bondy, B., Baghai, T.C., Minov, C., Schule, C., Schwarz, M.J., Zwanzger, P., et al. (2003) Substance P Serum Levels Are Increased in Major Depression: Preliminary Results. Biological Psychiatry, 53, 538-542.
http://dx.doi.org/10.1016/S0006-3223(02)01544-5

  
comments powered by Disqus

Copyright © 2019 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.