Intracellularly recorded response of rat striatal neurons in vitro to fenoldopam and SKF 38393 following lesions of midbrain dopamine cells.
The effect of long-term (6-19 weeks) 6-hydroxydopamine-induced (6-OHDA) lesions of midbrain dopamine cells on dopamine D1-like agonist-induced changes in the excitability of rat striatal neurons was investigated in vitro using tissue slices and intracellular recording techniques. Fenoldopam and (+/-)-SKF 38393 predominantly decreased excitability in control preparations including striatal neurons located contralateral to 6-OHDA injection sites and neurons obtained from rats receiving sham injections or no treatment. Fenoldopam also inhibited neurons ipsilateral to lesions of midbrain dopamine cells. (+/-)-SKF 38393, unlike fenoldopam, produced predominantly increases in the excitability of ipsilateral striatal neurons. Superfusion of the D1 receptor antagonist, SCH 23390, blocked fenoldopam-induced decreases in excitability but not the (+/-)-SKF 38393-induced excitation of neurons ipsilateral to the lesion. Sequential application of fenoldopam and quinpirole, a D2/D3 receptor agonist, produced responses to both drugs in a majority of neurons. The results demonstrate that inhibitory responses to fenoldopam are mediated by D1 receptors, while excitatory effects of (+/-)-SKF 38393 in the striatum ipsilateral to the lesion are apparently not dependent on D1 receptor activation. These findings also suggest that dopamine D1 and D2/D3 receptors are able to concurrently influence the excitability of striatal neurons in the dopamine deafferentated striatum. Similar regulation of striatal neurons in vivo may contribute to dopaminergic regulation of basal ganglia output and the ability of dopaminomimetic agents to ameliorate symptoms of dopaminergic deficiency in Parkinson's disease.
Twery
M J
MJ
Cellular Physiology and Neurotransmission Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
Thompson
L A
LA
Walters
J R
JR
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology*; D000818:Animals; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation; D004873:Ergolines / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D018818:Fenoldopam / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008839:Microelectrodes; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D016627:Oxidopamine / Q000494:pharmacology; D019257:Quinpirole; D051381:Rats; D017207:Rats, Sprague-Dawley
D018491:Dopamine Agonists; D004873:Ergolines; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D016627:Oxidopamine; D018818:Fenoldopam; D004298:Dopamine