2
Fear and Anxiety

"It is not obvious what is obvious"
Daniel Dennett

With a few exceptions, nearly all the anxiety-mediating agents (e.g. the beta-carbolines) found to date have as their site of action the benzodiazepine receptors (TAS; p 121). Beta-carboline ligands which bind to the benzodiazepine receptors induce in humans

"...intense inner strain and excitation, increased blood pressure and pulse, restlessness, increased cortisol and catecholamine release, and stereotyped rocking motions. The administration of anxiety-producing beta-carbolines to primates caused piloerection (hair raising) and struggling in the restraint chair, increased blood pressure and pulse, increased cortisol and catecholamine release, and increased vocalization and urination." (TAS p121)

         Again with a handful of exceptions, the anti-anxiety properties of alcohol, the barbiturates and the benzodiazepines (the 'minor tranquillisers': Valium etc) can be tied to a large, single, multifunctional receptor complex. This single neurochemical substrate includes a barbiturate- and ethanol-binding site, a chloride ion channel, and a binding site for neurotransmission. It has been shown that there are high-affinity saturable and specific receptors for the benzodiazepines in the vertebrate central nervous system. Following the landmark study of Nielsen, Braestrup and Squires (Evidence for a late Evolutionary Appearance of a Brain Specific Benzodiazepine Receptor, Brain Research 141 (1978) 342-466), persuasive evidence has accumulated that all vertebrates - including the bony fishes - have these receptors. Such receptors were found to be absent in all the invertebrate species tested (originally the woodlouse, earthworm, locust, lobster and squid); and also from the cartilaginous fishes.

        Inevitably, the full story is messier. As DeGrazia notes, the discovery of peripheral benzodiazepine-receptors with a presumably non-anxiety role [and also the development of 5HT1a mixed agonists such as buspirone with anti-anxiety properties], means the intricacies of the evolutionary story are vastly more complicated than any lightning sketch can show. Yet overall, there is strong evidence that all vertebrates, and some invertebrates, suffer anxiety and fear.