Despite important inconsistencies and contradictions, some plausible hypotheses circled around the noradrenergic system have been proposed and studied. The basis of most of these hypotheses is the assumption that the hyperreactivity of the sympathetic branch of the autonomous nervous system is due to some kind of dysregulation of noradrenergic system, especially at the level of alpha2 adrenoreceptors. Some argue that it is the locus ceruleus that is malfunctioning, through pathologic changes in the number or sensitivity of noradrenergic receptors, and consequently the peripheral noradrenergic system is affected. Others suggest that the symptomatology of panic disorder is due to the overreactivity of the entire system. It is also quite possible that the release or synthesis of norepinephrine and other catecholamines is affected (Nutt & Glue, 1989). Still another possibility is an insufficient parasympathetic control (George et al., 1989), even though evidence now exists contradicting such claim (Asmundson & Stein, 1994). Essentially, the pathology might involve any step in the destiny of the neurotransmitter.
It is clear that the questions "What generates panic attacks?" and "Why are some people susceptible to the development of the disorder" remain essentially unanswered and that the evidence is often contradictory and inconclusive. Part of the reason for such discrepancy might be simply attributable to various methodological problems, differences in experimental procedures, variation in the characteristics of the population studied (in terms of age, gender, weight, previous and current medication, length of withdrawal from medication etc.), imprecise detection techniques, differences among laboratories, measurement errors of all kinds and statistically significant effects that are not robust enough. Inconsistency in the definition of panic attack that varies from study to study and is usually arbitrary at least to some degree is another source of problems. One of the main difficulties in testing biochemical hypotheses is also the remarkable variability regarding the neurochemical parameters among subjects as well as within an individual across time. The other and most important part of the reason is probably the fact that the studies investigate different aspects of the panic disorder or else different subgroups of patients. Indeed, the possibility that the panic symptomatology is induced by different neurobiological dysfunctions must be envisaged. Various panic-provoking agents may produce the same symptomatology, perhaps with accent on certain clusters of symptoms typical for the specific agent. However, the mechanisms of their action might be quite different, even though with possibly common underlying mechanism; therefore, the neuropathways activated would reflect such variability.