Action of intravenously administered talipexole on the rat striatal neurons receiving excitatory input from nigral dopamine neurons.
Electrophysiological studies using rats anesthetized with chloral hydrate were performed to elucidate whether or not intravenously injected talipexole acted as a D2 receptor agonist on the striatal neurons in comparison with the action of bromocriptine. The activities of the striatal neurons were extracellularly recorded using a glass microelectrode attached along a seven-barreled micropipette, each barrel of which was filled with talipexole, bromocriptine, SCH23390 (D1 antagonist), domperidone (D2 antagonist), glutamate or 2 M NaCl. These drugs were iontophoretically applied to the immediate vicinity of the target neuron being recorded. The effects of talipexole and bromocriptine were examined on the neurons, whose spikes (induced by the stimulation of the substantia nigra pars compacta) were inhibited by the iontophoretic application of domperidone. Iontophoretic application of talipexole or bromocriptine increased spontaneous firing of these neurons and this increase in firing was also inhibited by iontophoretically applied domperidone. In the same neurons, intravenously administered talipexole (0.01, 0.02 and 0.04 mg/kg) dose-dependently increased firing, and this increase was inhibited by microiontophoretically applied domperidone, but not by SCH23390. On the other hand, the intravenous injection of bromocriptine (0.1, 0.2 and 0.4 mg/kg) also increased the firing rate. However, the increase was not dose-dependent and fluctuated; the firing transiently decreased during the increase in firing with intravenously administered bromocriptine. However, the bromocriptine-induced increase in firing was also suppressed by domperidone, and decrease in firing was inhibited by SCH23390. These findings suggest that talipexole acts as a D2 agonist on the striatal neurons receiving input from substantia nigra pars compacta and increases firing when intravenously applied.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, Hiroshima University School of Medicine, Japan.
H
H
Matsubayashi
T
T
Amano
Y
Y
Hongjing
Y
Y
Kohno
M
M
Sasa
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D001971:Bromocriptine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D007275:Injections, Intravenous; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000187:drug effects*; D013378:Substantia Nigra / Q000187:drug effects*
D001381:Azepines; D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D001971:Bromocriptine; C024763:talipexole