Skin conductance response after 6-hydroxydopamine lesion of central noradrenaline system in cats.

Absence of skin conductance response (SCR) is a psychophysiological sign frequently observed among schizophrenic patients. This alteration of electrodermal activity can be reproduced in cats and rats by intraventricular administration of 6-hydroxydopamine (6-OHDA), a neurotoxin selectively destroying catecholamine neurons. The finding appears to be quite consistent with the catecholamine hypothesis of schizophrenia. To determine which catecholamine system--the dopamine (DA) or the noradrenaline (NA)--is responsible for the induction of this abnormality, the same dose of 6-OHDA was microinjected to either the ventral tegmental area (VTA, n = 3), through which most DA fibers ascend, or to the ascending noradrenergic bundle (ANB, n = 3), through which most NA fibers ascend. Four cats remained intact as a control for later brain catecholamine estimation. The skin conductance of all pretreatment intact cats (n = 10) showed not only spontaneous fluctuations but also SCRs to auditory stimuli (5 kHz, 100 dB, 1 sec) which habituated with repetition. In contrast, ANB-lesioned cats showed a complete abolition of auditory SCRs, few spontaneous fluctuations, and a low basal skin conductance level. These abnormalities were statistically significant. On the other hand, no change was found in the skin conductance activity of the VTA-lesioned cats. Catecholamine estimation after the experiment confirmed selective destruction of the appropriate system corresponding to each type of lesion. These findings are discussed in the context of the DA or NA theory of schizophrenia, and involvement of the NA system in the pathogenesis of this illness is suggested.