The reasons why anxiety disorders manifest are not fully understood, although it is thought a disruption in the balance between opposing circuits responsible for interpretation of fearful stimuli, a process in which the amygdala is heavily involved, maybe key58. It is possible endogenous opioid signalling is one of the essential components that maintain balance within these ‘interpretation circuits', particularly during times of stress. If so, individual variability in fear and anxiety may result from differential expression of enkephalin. In fact, in a subpopulation of rats where stress strongly reduces ME expression in the amygdala, this was correlated with increased vulnerability to negative stress responses59. While opioid receptors and peptides are expressed and likely act in other subdivisions of the amygdala215660, the strong regulation of Im neurons by endogenous opioids is an appealing mechanism for opioid regulation of fear and anxiety behaviours. Further, since endogenously released opioid regulation is engaged by moderate synaptic activity, this suggests some of their effects on anxiety maybe via regulation of continuous information flow through dynamic Im-associated neural circuits. This is in contrast to the currently perceived role in which endogenous opioids both regulate and are released by a high-intensity trigger such as a synaptic plasticity event or learning processes. In addition, endogenously released opioids may also regulate the expression of previously established plasticity/learning traces. This additional role is important, as treatments for anxiety disorders are rarely able to preempt the initial learning but regulators of prior plasticity/learning could be valuable therapeutic options to reduce expression of fear and anxiety disorders.