Neuroscience and Behavioral Physiology. Vot. 28, No. 4. 1998 ADENYLATE CYCLASE SYSTEM OF THE RAT STRIATUM: REGULATORY PROPERTIES AND THE EFFECTS OF GANGLIOSIDES S. A. Plesneva, N. N. Nalivaeva, and I. A. Zhuravin The activity and regulatory properties of the adenylate cyclase system of the rat striatum were studied. Agents such as Gpp(NH)p, forskolin, and NaF were found to show classical in vitro stimulation of adenylate cyclase activity in the striatum membrane fraction. Dosage of rats with a preparation containing gangliosides (30 mg/kg, 6 i.p. injections) led to prolonged reductions in basal striatal adenylate cyclase activity. Two weeks after ganglioside administration, enzyme activity was reduced by 48% and remained lower than in controls (by 18%) even a month after injections. In vitro studies of the effects of gangliosides on adenylate cyclase activity in whole brain and striatal synaptosomes from rats showed that gangliosides have modulating actions on the adenylate cyclase system of the striatum, mainly due to changes in the catalytic function of the enzyme itself, and have no significant effect on the GTP-binding center of G-protein. Key words: Adenylate cyctase, gangliosides, Gpp(NH)p, forskolin, NaF, striatum, rat. cAMP is a universal second messenger which in nerve tissue mediates the actions of many extracellular regulatory signals (neurotransmitters, neuromodulators, neurohormones) [15] with significant effects on the integrative activity of neurons [6]. Among the enzymes determining the intracellular level of cAMP is adenylate cyclase, whose activity is in turn regulated via membrane-bound receptors linked with G-proteins [1, 5, 17]. Receptors linked to the adenylate cyclase system include adrenergic, muscarinic, adenosine, and dopaminergic receptors, as well as receptors for other biogenic amines [I]. The striatum, which is an integrative structure of the brain, has a wide spectrum of receptor systems [10], mediating the actions of a variety of agents on nerve cells through the adenylate cyclase system. Our previous investigations [2] showed a reduction in the level of adenylate cyclase activity in the cortex and striatum of rats trained to perform an operant reflex. Reductions in the activity of this enzyme depended on the animal's learning ability and were greater in well-trained animals. Dosage of animals with a preparation containing gangliosides (complex glycosphingolipids with neuritogenic and neurotrophic properties) led to improved learning and memory of the learned reflex [3], as well as a reduction in the threshold of sensitivity to cholinergic agonists which increased motor activity and tremor [20]. The mechanisms and causes of changes in adenylate cyclase activity when animals perform motor behavior remain unclear, as does the role of gangliosides in these processes. The aim of the present work was to study the effects of gangliosides on the activity and regulatory properties of the adenylate cyclase system of the rat striatum in vivo and in vitro. Studies on the regulatory properties of adenylate cyclase were conducted using agents such as Gpp(NH)p, forskolin, and NaF. METHODS Studies were performed using three-month-old male Wistar rats (150-170 g). Rats received i.p. gangliosides at a dose of 30 mg in 0.2 ml of physiological saline. Animals were injected six times over two weeks. Gangliosides were prepared from cattle brains as described by Folch et al. [9] as modified by Suzuki [18]. N-Acetylneuraminic acid contents in lyophilized preparations amounted to 28%. In vitro experiments used ganglioside GM1 (Sigma). I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44 M. Torez Prospekt, 194223 St. Petersburg, Russia. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 83, No. 1-2, pp. 90-95, January-February, 1997. Original article submitted July 5, 1996; revision submitted October 9, 1996. 392 0097-0549/98/2804-0392520.00 9 Plenum Publishing Corporation