Abstract
The effects of three selective D4 antagonists [CP-293,019, L-745,870, and Ro 61-6270] and two putative selective D4 agonists [CP-226,269 and PD 168077] were compared with those of the generic D2-like [D2L/S,D3, D4] antagonist haloperidol to identify any characteristic “ethogram,” in terms of individual topographies of behavior within the natural rodent repertoire, as evaluated using ethologically based approaches. Among the D4 antagonists, neither L-745,870 (0.0016–1.0 mg/kg) nor Ro 61-6270 (0.2–25.0 mg/kg) influenced any behavior; whereas, CP-293,019 (0.2–25.0 mg/kg) induced episodes of nonstereotyped sniffing, sifting, and vacuous chewing; there were no consistent effects on responsivity to the D2-like agonist RU 24213. Among the putative D4 agonists, CP-226,269 (0.2–25.0 mg/kg) failed to influence any behavior; whereas, PD 168077 (0.2–25.0 mg/kg) induced nonstereotyped shuffling locomotion with uncoordinated movements, jerking, and yawning, which were insensitive to antagonism by CP-293,019, L-745,870, or haloperidol. These findings fail to indicate any “ethogram” for selective manipulation of D4 receptor function at the level of the interaction between motoric and psychological processes in sculpting behavioral topography over habituation of exploration through to quiescence and focus attention on social, cognitive, or other levels of examination.
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Acknowledgements
These studies were supported by the Research Committee of the Royal College of Surgeons in Ireland and the Higher Education Authority. We thank Hoechst-Marion-Roussel, Merck Sharpe & Dohme, Parke-Davis, Pfizer and Roche for kindly making drugs available to us.
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Clifford, J., Waddington, J. Topographically Based Search for an “Ethogram” Among a Series of Novel D4 Dopamine Receptor Agonists and Antagonists. Neuropsychopharmacol 22, 538–544 (2000). https://doi.org/10.1016/S0893-133X(99)00141-4
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DOI: https://doi.org/10.1016/S0893-133X(99)00141-4
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