Brain dopamine D-2 receptor mechanisms in spontaneously hypertensive rats.
Brain dopaminergic function was studied in spontaneously hypertensive rats (SHR) with the selective dopamine D-2 antagonist sulpiride. Sulpiride dose-dependently inhibited locomotor activity of normotensive Wistar-Kyoto rats (WKY). SHR showed an increase in locomotor activity in response to low doses of sulpiride, whereas no effect was observed of higher doses. In a two-bottle salt-preference test, WKY showed increased preference for an 0.9% saline solution after treatment with sulpiride, whereas total fluid intake remained the same. In SHR, sulpiride influenced neither salt-preference nor total fluid intake. SHR and WKY with a unilateral lesion of the median forebrain bundle showed similar turning behaviour in response to treatment with amphetamine. Pretreatment with 100 mg/kg sulpiride virtually abolished amphetamine-induced turning in WKY, but had little effect in SHR. Sulpiride dose-dependently increased serum prolactin concentrations in WKY and SHR. However, the increase was significantly greater in SHR. Dopamine D-2 receptor binding was measured with in vitro autoradiography, using [125I]-sulpiride as the ligand. Binding density was similar in the caudate nucleus and substantia nigra of SHR and WKY brain. Concentrations of the dopamine metabolites DOPAC and HVA, but not of dopamine itself, were significantly increased in frontal cortex, striatum and hypothalamus after treatment with 100 mg/kg sulpiride. There were no significant differences between SHR and WKY in the increase in the DOPAC/DA and HVA/DA ratio. These data show that SHR show differential changes in their response to central dopamine D-2 blockade when compared to WKY. Thus, in some tests (locomotor activity after high doses, salt preference, turning behaviour), SHR respond less to sulpiride.(ABSTRACT TRUNCATED AT 250 WORDS)
Van den Buuse
M
M
Marion Merrell Dow Research Institute, Strasbourg, France.
Jones
C R
CR
Wagner
J
J
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001552:Benzazepines / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007457:Iodine Radioisotopes; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism; D009928:Organ Specificity; D011388:Prolactin / Q000097:blood; D016548:Prosencephalon / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011921:Rats, Inbred WKY / Q000502:physiology; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012701:Serotonin / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects; D013469:Sulpiride / Q000378:metabolism / Q000494:pharmacology*; D013649:Taste
C049558:8-iodo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol; D001552:Benzazepines; D007457:Iodine Radioisotopes; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D013469:Sulpiride; D011388:Prolactin; D003891:Desipramine; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid