Animal studies indicate that the local anesthetic procaine specifically activates limbic structures. Human studies suggest that acute intravenous procaine induces a range of psychosensory and emotional experiences associated with increased temporal lobe fast activity, decreased occipital alpha activity, and increases in ACTH, cortisol and prolactin, but not growth hormone. The effects of acute intravenous procaine on regional cerebral blood flow (rCBF) measured with oxygen-15 water and positron emission tomography (PET) have been studied in 17 patients with mood disorders and 32 healthy volunteers. Data analysis with statistical parametric mapping (SPM) has revealed that procaine sig- nificantly increases rCBF bilaterally in the anterior temporal lobes (aTL), inferior frontal lobes (iFL) and anterior cingulate gyri (aCG) in an amygdalofugal pattern. Visual inspection of individual PET subtraction images with co-registered magnetic resonance images (MRI) qualitatively confirmed this pattern. Subjects with intense procaine- induced visual hallucinations, compared with those without, had increased rCBF in the occipital (visual) cortex in addition to more robust amygdalofugal and global activation. Compared with those without, subjects with intense procaine-induced anxiety had increased amygdalofugal activation; those with intense procaine-induced euphoria had more intense activation of the septal area and hypothalamus. These data also suggest that amygdalofugal limbic and paralimbic structures in the aTL, iFL, and aCG may comprise important elements of the neural substrate of emotional experiences. Furthermore, patients with mood disorders compared with controls had not only decreased resting rCBF in the frontal lobes and left amygdala, but also blunted amygdalofugal rCBF responses to procaine, even though they had a similar range of clinical responses. Such anterior temporal and frontal hypofunction could underlie the emotional and cognitive disturbances observed in affective disorders.
