Invited Symposium: MAOIs: Mulptiple Effects and Sites of Action
Szechtman, H. (Department of Psychiatry and Behavioral Neurosciences, McMaster University, Canada)
Repeated administration of the D2/D3 agonist quinpirole, results in locomotor sensitization, which is a progressive augmentation of the locomotor response to the drug. Studies conducted by Levant et al. (JPET 278: 145, 1996) have opened the possibility that, at least for quinpirole, a novel binding site may be implicated in the process of locomotor sensitization. Specifically, in vitro findings in rat striatal membranes have demonstrated that monoamine oxidase inhibitors (MAOIs), such as clorgyline, inhibit the binding of quinpirole, but not that of the D2 receptor antagonist spiperone. These results suggest that certain MAOIs possess a unique affinity for a novel MAOI-diaplaceable quinpirole binding site (MQB), that is either labeled by quinpirole, or which modulates quinpirole binding at D2-like receptors. Behavioral studies have demonstrated that chronic clorgyline administration blocks the development and attenuates the expression of quinpirole-induced locomotor sensitization, indicating that both the development and expression of quinpirole-induced locomotor sensitization are MAOI sensitive. These findings suggest that clorgyline's blockade of quinpirole-induced locomotor sensitization may be attributed to its action at the MQB site. Furthermore, recent studies have demonstrated that MAOIs such as moclobemide, which possess little affinity for the MQB site, do not block the development or expression of quinpirole-induced locomotor sensitization. Based on these findings, it is hypothesized that stimulation of the MQB site is necessary for the development and expression of quinpirole-induced locomotor sensitization.
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|Culver, K; Szechtman, H.; (1998). Locomotor Sensitization to Quinpirole: Role of a MAOI Sensitive Site. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/levant/culver0524/index.html|
|© 1998 Author(s) Hold Copyright|