Naunyn-Schmiedeberg's Arch. Pharmacol. 308, 155-157 (1979) Naunyn-Schmiedeberg's Archivesof Pharmacology 9 by Springer-Verlag 1979 Foot-Shock Stress Accelerates Non-Striatal Dopamine Synthesis Without Activating Tyrosine Hydroxylase A. H. Tissari *, A. Argiolas, F. Fadda **, G. Serra, and G. L. Gessa Institutes of Pharmacology and Physiology **, Universitfi di Cagliari, Via Porcell 4, 1-09100 Cagliari, Italy Summary. Electric foot-shock stress (20 min) increases DOPAC content in the frontal cortex (by about 80 %) and in the nucleus accumbens (by 35 %) but not in the striatum. However, foot shock stress failed to modify the kinetic properties of tyrosine hydroxylase (Vmax,K~ for DMPH 4 cofactor) in any of the above areas. Similar results were obtained in rats in which noradrenergic terminals in the n. accumbens and in the frontal cortex had been eliminated by injection of 6-OH-dopamine into the ascending dorsal noradrenergic bundle. The results support the hypothesis that limbic and cortical DA is involved in emotional states and indicate that DA synthesis may be regulated independently from changes in the kinetics properties of tyrosine hydroxylase. Key words: Foot-shock stress - DOPAC - Dopamine - Tyrosine hydroxylase. Introduction Different kinds of stress increase brain dopamine (DA) synthesis in rats and mice (Thierry et al., 1968; Bliss and Ailion, 1971). Recently, Thierry et al. (1976) have shown that foot shock stress selectively augments DA synthesis in the mesolimbic and, more effectively, in the mesocortical dopaminergic system, but that is in- effective in other brain areas. In different experimental conditions increase in DA synthesis is associated with, and is considered to be dependent on, changes in the kinetic properties of tyrosine hydroxylase (TH). Thus, neuroleptic administration or electrical stimulation of the nigro-striatal dopaminergic pathways results both Send offprint requests to G. L. Gessa at the above address * Permanent address: Institute of Pharmacology, University of Helsinki, Finland in increased DA synthesis, and in an activation of TH, characterized by an increased affinity for its cofactor (Zivkovic et al., 1974). However, we have recently shown that neuroleptics still increase DA synthesis but lose their ability to activate TH after destruction of postsynaptic receptors with kainic acid, suggesting the existence of two mechanisms regulating DA synthesis in vivo: one operating by means of postsynaptic DA- receptors and regulating DA synthesis through the activation of TH, the other acting via presynaptic DA- receptors controlling DA synthesis independently from TH activation (Di Chiara et al., 1978). In order to clarify whether the two mechanisms might evidentiated under non-pharmacological conditions, we compared the effect of foot-shock stress on TH activity and on 3,4-dihydroxyphenylacetic acid (DOPAC) level, the primary DA metabolite. When DA levels are un- changed, changes in DOPAC concentrations often reflect parallel changes in the synthesis of DA (Roth et al., 1976; Roffler-Tarlov et al., 1971). The present results show that electrical foot-shock selectively increases DOPAC levels in the frontal cortex and in the nucleus accumbens but fails to activate TH in these areas. Material and Methods Male Sprague Dawley rats, weighing 180 - 210 g were housed at 24 ~C with lights on from 6.00 to 18.00 and had water and standard laboratory food ad libitum. Stress consisted of a series of electrical foot shocks delivered in individual cages, with floors made of brass rods. Shocks were provided by a stimulator which delivered a shock of 2mA every 320ms with 160ms duration for a total period of 20nain. Animals were killed immediately after foot shock. Brains were rapidly removed and frontal cortex, nucleus accumbens and striatum were dissected on ice as described by Westerink and Korf (1976). TH activity was measured according to the method of Waymire et al. (1971) modified by Zivkovic et al. (1974). Norepinephrine (NE), DA and DOPAC were assayed in an aliquot of the same homogenate used for TH assay, according to a slight modification of the method of Argiolas and Fadda (1978). 0028-1298/79/0308/0155/$01.00