Locomotor Sensitization of Dopamine Receptors by Their Agonists Quinpirole and SKF-38393, During Maturation and Aging in Rats

Document Type

Article

Publication Date

12-1-1997

Description

Our laboratories have been investigating the reactivity of central dopamine D1 and D2/D3 receptors by their corresponding dopamine agonists (SKF-38393 and quinpirole), during development and aging in rats. By evaluating the number of oral movements (a parameter for D1 receptor activation after SKF-38393) and the number of yawns (as a parameter for D3 activation after quinpirole), we demonstrated that not only was there a dose-response activity for both drugs in the two parameters tested, but that the D3 activity was enhanced with the rats' development and aging, due to life-long persisting D3 supersensitivity. In the present study we checked whether D2 and D1 receptors were also sensitized at old age, by measuring behavioral parameters characteristic to D2 (locomotor activity and rearings) and to D1 (grooming time). In the long-term study, male Wistar rats were challenged for 18 months with increasing doses of either SKF-38393, quinpirole or saline. At the age of 19 months they were given a single injection of either drug or saline. In the short-term study, male and female rats were given four single injections of either SKF-38393, quinpirole or saline, with one week intervals, and locomotor time and number of rearings recorded. Long-term quinpirole was found to induce supersensitivity of the D2 receptor complex, demonstrated by both enhanced locomotor time and rearing behavior, while long-term SKF-38393 treatment activated the D1 receptors, as evaluated by grooming time. Short-term quinpirole enhanced supersensitivity of the D2 receptors only in female rats, as assessed by increasing both locomotor time and rearing behavior, reiterating previous results on sex-dependent monoaminergic reactivity.

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