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Do not bury thirty years of avoidance findings

Molecular Psychiatry volume 23, pages 497–498 (2018)Cite this article

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The claim of LeDoux et al.1 about the “death” of research interest on avoidance conditioning is not fully justified, and some relevant nuances may be added. The research on avoidance behaviour in rodents during the last 30 years was alive and productive: over 30 papers on pharmacological, behavioural and genetic mediators of two-way (shuttle box) avoidance (refs.2, 3, 4, 5), came from our lab, focused mostly on disclosing the role that anxiety plays in the approach-avoidance conflict involved in the acquisition of that task.2, 3, 4, 5, 6 Many other studies provided pharmacological and neurobehavioral support to the mediating role of anxiety during two-way avoidance learning (the main focus of LeDoux et al. review; see refs. 4, 5). We and others have shown that anxiolytic compounds (benzodiazepines, triazolobenzodiazepines, barbiturates and ethanol) and anxiety-reducing behavioural treatments accelerate the transition from pavlovian threat reactions (conditioned freezing) to instrumental avoidances.2, 3, 4, 5, 8 Critical for the contention that the task is driven by the anxiety coming from an approach-avoidance conflict is the fact that anxiety-inducing treatments, such as pro-conflict drugs, withdrawal from chronic diazepam or ethanol, or anxiogenic/stressful behavioural treatments impair the acquisition of shuttle box avoidance.4, 5, 8, 9, 10

A second point that is not addressed by that review deserves attention. Any proposal of a detailed circuitry for approach-avoidance conflict (including two-way avoidance acquisition), not taking into account the role of the septo-hippocampal system will be incomplete.6, 11, 12, 13 The septo-hippocampal-focused tradition of research on the neural bases of approach-avoidance conflicts (involving anxiety and fear) has actually evolved in parallel to the developments of the amygdala-centred tradition. Gray and McNaughton,6 after marshalling dozens of lesion studies, proposed that the transition from passive (freezing) to active responses during approach-avoidance conflict (of which two-way avoidance task is a particular case), is regulated by activity of the septo-hippocampal system. The highest its activity the more passive reactions: more freezing and low probability of active “avoidances”. Accordingly, septo-hippocampal lesions or (more recently) ventral hippocampal lesions, like anxiolytic drug treatments, facilitate approach-avoidance conflict resolution by increasing (approach) active responses or decreasing passive avoidance.6, 11, 12, 13 Anxiolytics act on the hippocampal system (although also in other regions, such as the amygdala) by disrupting theta rhythm, which is known to be linked to anxiety.6, 12 The septo-hippocampal system appears to act as a comparator under conditions of competing goals (approach-avoidance conflict) to select a response.6, 12 One way, but not necessarily the only way to do that, might be through ventral hippocampus connections with the amygdala (and related structures), enabling the execution of appropriate responses.6, 11, 12

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References

  1. LeDoux JE, Moscarello J, Sears R, Campese V . The birth, death and resurrection of avoidance: a reconceptualization of a troubled paradigm. Mol Psychiatry 2017; 22: 24–36.

    Article  CAS  Google Scholar 

  2. Fernandez-Teruel A, Escorihuela RM, Núñez JF, Zapata A, Boix F, Salazar W et al. The early acquisition of two-way (shuttle-box) avoidance as an anxiety-mediated behavior: psychopharmacological validation. Brain Res Bull 1991; 26: 173–176.

    Article  CAS  Google Scholar 

  3. Escorihuela RM, Tobeña A, Driscoll P, Fernandez-Teruel A . Effects of training, early handling, and perinatal flumazenil on shuttle box acquisition in Roman low-avoidance rats: toward overcoming a genetic deficit. Neurosci Biobehav Rev 1995; 19: 353–367.

    Article  CAS  Google Scholar 

  4. Vicens-Costa E, Martinez-Membrives E, López-Aumatell R, Guitart-Masip M, Cañete T, Blázquez G et al. Two-way avoidance acquisition is negatively related to conditioned freezing and positively associated with startle reactions: a dissection of anxiety and fear in genetically heterogeneous rats. Physiol Behav 2011; 103: 148–156.

    Article  CAS  Google Scholar 

  5. Río-Álamos C, Oliveras I, Cañete T, Blázquez G, Martínez-Membrives E, Tobeña A et al. Neonatal handling decreases unconditioned anxiety, conditioned fear, and improves two-way avoidance acquisition: a study with the inbred Roman high (RHA-I)- and low-avoidance (RLA-I) rats of both sexes. Front Behav Neurosci 2015; 9: 174.

    Article  Google Scholar 

  6. Gray JA, McNaughton N . The Neuropsychology of anxiety: An enquiry into the function of the septo-hippocampal system, 2nd ed. Oxford University Press: Oxford, 2000; 444p.

    Google Scholar 

  7. Aguilar R, Gil L, Fernández-Teruel A, Tobeña A . Genetically-based behavioral traits influence the effects of Shuttle Box avoidance overtraining and extinction upon intertrial responding: a study with the Roman rat strains. Behav Processes 2004; 66: 63–72.

    Article  Google Scholar 

  8. Escorihuela RM, Tobeña A, Fernández-Teruel A . Environmental enrichment reverses the detrimental action of early inconsistent stimulation and increases the beneficial effects of postnatal handling on shuttlebox learning in adult rats. Behav Brain Res 1994; 61: 169–173.

    Article  CAS  Google Scholar 

  9. Criswell HE, Breese GR . Similar effects of ethanol and flumazenil on acquisition of a shuttle-box avoidance response during withdrawal from chronic ethanol treatment. Br J Pharmacol 1993; 110: 753–760.

    Article  CAS  Google Scholar 

  10. Lacerra C, Martineja ID, Bustos SG, Molina VA . Benzodiazepine withdrawal facilitates the subsequent onset of escape failures and anhedonia: influence of different antidepressant drugs. Brain Res 1999; 819: 40–47.

    Article  CAS  Google Scholar 

  11. Bannerman DM, Rawlins JN, McHugh SB, Deacon RM, Yee BK, Bast T et al. Regional dissociations within the hippocampus—memory and anxiety. Neurosci Biobehav Rev 2004; 28: 273–283.

    Article  CAS  Google Scholar 

  12. McNaughton N, Corr PJ . A two-dimensional neuropsychology of defense: fear/anxiety and defensive distance. Neurosci Biobehav Rev 2004; 28: 285–305.

    Article  Google Scholar 

  13. Ito R, Lee AC . The role of the hippocampus in approach-avoidance conflict decision-making: evidence from rodent and human studies. Behav Brain Res 2016; 313: 345–357.

    Article  Google Scholar 

  14. Bach DR, Guitart-Masip M, Packard PA, Miró J, Falip M, Fuentemilla L et al. Human hippocampus arbitrates approach-avoidance conflict. Curr Biol 2014; 24: 541–547.

    Article  CAS  Google Scholar 

  15. LeDoux J . Anxious. Using the brain to understand and treat fear and anxiety. Penguin Books: New York, 2015; 454p.

    Google Scholar 

  16. Moreno M, Cardona D, Gómez MJ, Sánchez-Santed F, Tobeña A, Fernández-Teruel A et al. Impulsivity characterization in the Roman high- and low-avoidance rat strains: behavioral and neurochemical differences. Neuropsychopharmacology 2010; 35: 1198–1208.

    Article  Google Scholar 

  17. Giorgi O, Piras G, Corda MG . The psychogenetically selected Roman high- and low-avoidance rat lines: a model to study the individual vulnerability to drug addiction. Neurosci Biobehav Rev 2007; 31: 148–163.

    Article  CAS  Google Scholar 

  18. Tournier BB, Steimer T, Millet P, Moulin-Sallanon M, Vallet P, Ibañez V et al. Innately low D2 receptor availability is associated with high novelty-seeking and enhanced behavioural sensitization to amphetamine. Int J Neuropsychopharmacol 2013; 16: 1819–1834.

    Article  CAS  Google Scholar 

  19. Rio-Alamos C, Oliveras I, Piludu MA, Gerbolés C, Cañete T, Blázquez G et al. Neonatal handling enduringly decreases anxiety and stress responses and reduces hippocampus and amygdala volume in a genetic model of differential anxiety: behavioral-volumetric associations in the Roman rat strains. Eur Neuropsychopharmacol 2017; 27: 146–158.

    Article  CAS  Google Scholar 

  20. Fadok JP, Krabbe S, Markovic M, Courtin J, Ch Xu, Massi L et al. A competitive inhibitory circuit for selection of active and passive fear responses. Nature 2017; 542: 96–100.

    Article  CAS  Google Scholar 

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Acknowledgements

The authors are supported by grants PSI2013-41872-P and 2014SGR-1587. The authors sincerely thank the anonymous reviewers of this paper for their particularly constructive criticisms and comments.

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  1. Department of Psychiatry and Forensic Medicine (Medical Psychology Unit), Institute of Neurosciences, School of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain

    A Fernández-Teruel & A Tobeña

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Correspondence to A Fernández-Teruel.

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Fernández-Teruel, A., Tobeña, A. Do not bury thirty years of avoidance findings. Mol Psychiatry 23, 497–498 (2018). https://doi.org/10.1038/mp.2017.209

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