Dopamine: biphasic dose responses.
The present article indicates that dopamine and/or its agonists induce biphasic dose-response relationships for numerous endpoints. These include locomotion, pain sensitivity, blood pressure, prolactin secretion, oxytocin release, heart rate, memory, and neuronal adenylate cyclase activity. Biphasic responses were reported predominantly with male Sprague-Dawley rats, but also with mice, dogs, monkeys, and humans. Regardless of the model or endpoint the maximum changes from the control were always modest being within the 10 to 80% range. The range of stimulatory responses was quite variable, extending from slightly greater than a factor of 10 for the endpoints such as memory, pain-vocalization, and diastolic blood pressure to the 10(6) range for prolactin release and the 10(8) range for oxytocin release. Mechanistic studies suggested that the stimulatory and inhibitory effects of dopamine are mediated by different receptors or receptor subtypes having opposite actions and different ligand affinities.
Calabrese
E J
EJ
Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, Amherst 01003, USA. edwardc@schoolph.umass.edu
D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004285:Dogs; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000882:Haplorhini; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008024:Ligands; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000201:enzymology; D010121:Oxytocin / Q000378:metabolism; D017288:Pain Threshold / Q000187:drug effects*; D011388:Prolactin / Q000378:metabolism; D011618:Psychotic Disorders / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000502:physiology*
D002316:Cardiotonic Agents; D008024:Ligands; D011954:Receptors, Dopamine; D010121:Oxytocin; D011388:Prolactin; D000262:Adenylyl Cyclases; D004298:Dopamine