Effects of locally applied D1 and D2 agonists on striatal neurons with 6-OHDA and pertussis toxin lesions.
Electrophysiological recordings were performed on caudate neurons in rats with dopamine (DA) depleted striatum in combination with pertussis toxin (PT) lesions. Pertussis toxin inactivates the G protein coupled to D2 receptors. DA depletions were performed by unilateral injections of 6-hydroxydopamine (6-OHDA). After the 6-OHDA lesion, rats were challenged with low doses of apomorphine. When a double peak rotational pattern was stable over repeated rotational tests, PT was injected into striatum ipsilateral to the DA depleted side. Two days after the PT injections extracellular recordings with local applications of the D1 agonist SKF 38393 and the D2 agonist N-0437 were performed. Spontaneous firing rates, measured before drug application, were elevated in animals with both 6-OHDA and 6-OHDA/PT combination of lesions. In rats with only 6-OHDA lesions, a supersensitivity to N-0437 was observed, while no significant change in response to the D1 agonist was detected. Recordings from caudate neurons in rats with a combination of 6-OHDA and PT resulted in no response to the D2 agonist. However, a subsensitivity to the D1 agonist was detected and only 60% of neurons were inhibited by SKF 38393. Taken together, these data suggest an interaction between the D1 and D2 receptors, which is revealed only after an upregulation of the D2 receptors and subsequent blockade of D2 mediated effects.
Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden.
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Strömberg
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Bickford-Wimer
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002421:Caudate Nucleus / Q000166:cytology / Q000187:drug effects; D003342:Corpus Striatum / Q000166:cytology* / Q000187:drug effects; D015259:Dopamine Agents / Q000494:pharmacology*; D005260:Female; D009422:Nervous System Diseases / Q000139:chemically induced / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects*; D016627:Oxidopamine; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000502:physiology*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013238:Stereotaxic Techniques; D013563:Sympathectomy, Chemical; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D010566:Virulence Factors, Bordetella
D015259:Dopamine Agents; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; D010566:Virulence Factors, Bordetella; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C047508:rotigotine; D016627:Oxidopamine; D037342:Pertussis Toxin; D001058:Apomorphine