Developmental rodent models of fear and anxiety: from neurobiology to pharmacology

Abstract

Anxiety disorders pose one of the biggest threats to mental health in the world, and they predominantly emerge early in life. However, research of anxiety disorders and fear-related memories during development has been largely neglected, and existing treatments have been developed based on adult models of anxiety. The present review describes animal models of anxiety disorders across development and what is currently known of their pharmacology. To summarize, the underlying mechanisms of intrinsic 'unlearned' fear are poorly understood, especially beyond the period of infancy. Models using 'learned' fear reveal that through development, rats exhibit a stress hyporesponsive period before postnatal day 10, where they paradoxically form odour-shock preferences, and then switch to more adult-like conditioned fear responses. Juvenile rats appear to forget these aversive associations more easily, as is observed with the phenomenon of infantile amnesia. Juvenile rats also undergo more robust extinction, until adolescence where they display increased resistance to extinction. Maturation of brain structures, such as the amygdala, prefrontal cortex and hippocampus, along with the different temporal recruitment and involvement of various neurotransmitter systems (including NMDA, GABA, corticosterone and opioids) are responsible for these developmental changes. Taken together, the studies described in this review highlight that there is a period early in development where rats appear to be more robust in overcoming adverse early life experience. We need to understand the fundamental pharmacological processes underlying anxiety early in life in order to take advantage of this period for the treatment of anxiety disorders.

The impact of early postnatal environmental enrichment on maternal care and offspring behaviour following weaning

“…This high baseline anxiety could possibly account for a ceiling effect, where no further increase in anxiety could be induced. As of to date, there is little knowledge about anxiety-related behaviour in rats during the immediate post-weaning period, and the underlying neurobiological mechanisms are most likely not fully matured yet (Ganella and Kim 2014). The discrepancies between open field and plus maze results warrant further research as aspects of anxiety related behaviours could possibly mature at different times during the postnatal period.…”

Ontogeny of memory: An update on 40 years of work on infantile amnesia

“…Since the seminal review by Spear (2000), rodent adolescence has been broadly defined to be P28 -P60, an age range utilised by many preclinical studies of anxiety and addiction [61][62][63][64]. These redefined developmental stages have already been referred to in previous papers (e.g., [65,66]) and are summarised in Figure 1. These definitions will be used throughout this review with the hope that they will become more widely adopted within the field of developmental neurobiology.…”

A Window on the Study of Aversive Instrumental Learning: Strains, Performance, Neuroendocrine, and Immunologic Systems

“…At first glance, this decrease in corticosterone is contrary to the concept of stress research because evidence predominately indicates an increase in corticosterone levels as a physiological response to stress (King and Hegadoren, 2002; Brush, 2003; Steimer and Driscoll, 2003; Lightman, 2008; Ganella and Kim, 2014; Spiga et al, 2015). …”