Biphasic Effects of D3-Receptor Agonists, 7-OH-DPAT anD PD128907, on the D1-Receptor Agonist-Induced Hyperactivity in Mice.

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  • Mori Tomohisa
    Drug Discovery, Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama 222, Japan
  • Murase Kenshi
    Drug Discovery, Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama 222, Japan
  • Tanaka Jiro
    Drug Discovery, Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama 222, Japan
  • Ichimaru Yasuyuki
    Drug Discovery, Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama 222, Japan

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  • Biphasic Effects of D3 Receptor Agonist

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Abstract

Effects of D3-receptor agonists, 7-OH-DPAT and PD128907, on the D1-receptor agonist SKF81297-induced hyperactivity in mice were examined. 7-OH-DPAT and PD128907 significantly suppressed the SKF81297-induced hyperactivity at low doses, but significantly potentiated the hyperactivity at high doses. These D3-agonists alone had no effect on the motor activity. A κ-receptor agonist that reduces dopamine release had no effect on the SKF81297-induced hyperactivity. These results suggest that lower doses of 7-OH-DPAT and PD128907 may negatively influence the D1-receptor mediated behaviors via post synaptic D3-receptors. On the other hand, higher doses of these compounds may positively influence these behaviors via D2 or D3-receptors.

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