Ro4-1284 (2-Ethyl-1,3,4,6,7,llb-hexahydro-3-isobutyl-9,10-dimethoxy-2H-benzo[a] quinolizin-2-ol hydrochloride), a benzoquinolizine, is a potent dopamine depletion agent whose acute and chronic administration results in a (1) deterioration of learning in the Morris Water Maze and passive avoidance tasks, (2) decrease in locomotion and rearing, (3) intense hypothermia, and (4) decrease in the percentage of polyunsaturated fatty acids and an increase in the level of cholesterol in neuronal membranes. Pretreatment with a specific mixture of free polyunsaturated fatty acids prevents most of the behavioral, physiological, and biochemical effects of Ro4-1284 except for rearing. We propose that the dopamine-mediated functions tested in this study are dependent on the interaction of intact dopamine D1 and D2 receptors. Rearing, which is controlled only by dopamine D1 receptors, remained, therefore, unaffected. Our hypothesis is that SR-3 exerts its beneficial effects by normalizing the structure and function of the neuronal membrane and by restoring dopamine D2 receptor functions. Copyright (C) 1999 Elsevier Science B.V.
Bibliographical noteFunding Information:
This research was supported by the K. Ginsburg Chair for Research into Alzheimer's Disease and by the William Farber Center for Alzheimer Research. We would like to thank Dr. J. Sepinwall (Hoffman LaRoche, Nutley, NJ, USA) for his generosity in supplying us with Ro4-1284.
- Linolenic acid
- Morris Water Maze
- Passive avoidance
- α-Linolenic acid