Serotonergic system and panic/anxiety
Serotonin seems to play a role in the biopathology of panic disorder even though its contribution is most likely far less important than that of norepinephrine. The serotonergic hypothesis of panic disorder suggests that panic attacks are partially due to a dysregulation at the level of the serotonergic pathways. Raphé nucleus, a midbrain structure with high concentration of serotonergic neurons, projects to locus ceruleus, and has an inhibitory influence on the activity of noradrenergic neurons (Meltzer, 1987). Substantial evidence exists today to support the implication of serotonin in anxiety disorders, especially obsessive-compulsive. Patients with obsessive-compulsive disorder respond best and exclusively to antidepressants that inhibit reuptake of serotonin, such as clomipramine. Murphy & Pigott (1990) have presented evidence suggesting that the anxiolytic effects of benzodiazepines might also be related to serotonergic activity. In addition to it, panic disorder and obsessive compulsive patients reported an exacerbation of symptoms when they received serotonin precursors tryptophan and 5-HTP, serotonin receptors' agonist m-chlorophenylpiperazine and flenfluramine, a drug that increases the synaptic availability of serotonin (Murphy & Pigott, 1990, Den Boer & Westenberg, 1990, Targum, 1990, Kahn & Van Praag, 1988). It is thus possible that an altered serotonergic transmission is one of the elements that are implicated in anxiety and panic. Although serotonin may be involved in the panic attacks, it is unlikely that it would be the main dysregulation found in panic patients. Panic disorder patients respond to a larger range of medication than those with obsessive compulsive disorder. What might turn out to be important is the interaction between the serotonergic and noradrenergic systems. As Gorman et al. (1989) suggest, panic attacks might be triggered due to an excessive excitability of locus ceruleus, chemoreceptors in medulla or raphé nucleus, condition that they expect to be inherited. These brain regions would be excited by lower than normal concentrations of neurotransmitters, toxins, lactate, CO2 or other agents.