Topographically based search for an "Ethogram" among a series of novel D(4) dopamine receptor agonists and antagonists.
The effects of three selective D(4) antagonists [CP-293,019, L-745, 870, and Ro 61-6270] and two putative selective D(4) agonists [CP-226,269 and PD 168077] were compared with those of the generic D(2)-like [D(2L/S),D(3), D(4)] 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 D(4) 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 D(2)-like agonist RU 24213. Among the putative D(4) 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 D(4) 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.
Clifford
J J
JJ
Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin, Ireland.
Waddington
J L
JL
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology*; D001931:Brain Mapping; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D008297:Male; D011618:Psychotic Disorders / Q000188:drug therapy / Q000503:physiopathology; D011719:Pyrazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D050638:Receptors, Dopamine D4
C099630:3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-1H-pyrrolo(2,3-b)pyridine; C111732:CP 293019; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; C493601:Drd4 protein, rat; D011719:Pyrazines; D011725:Pyridines; D011743:Pyrimidines; D011758:Pyrroles; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4