Behavioral and electrophysiological effects of 5-HT in globus pallidus of 6-hydroxydopamine lesioned rats.
Anatomical studies have shown that the globus pallidus receives abundant 5-hydroxytryptamine (5-HT) innervations from raphe nuclei. 5-HT may occupy an important position in the modulation of motor function through its affect on the activity of globus pallidus. In the present study, intrapallidal microinjection of 5-HT (0.1 mM) alone did not induce any motor behavior or postural asymmetry in the unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats. However, when infused concomitantly with a low dose of 3, 4-dihydroxyphenylalanine (L-DOPA, 3 mg/kg i.p.), which itself can induce modest contralateral rotational behavior, 5-HT significantly potentiated the number of contralateral rotations. To elucidate the cellular mechanism, in vivo extracellular recordings were performed to examine the effects of 5-HT on globus pallidus neurons. In normal rats, the predominant effect of micropressure ejection of 5-HT on pallidal neurons was excitation. In 6-OHDA-lesioned rats, although 5-HT increased the firing rate in most pallidal neurons, 5-HT-induced inhibitory effects was stronger than that on the unlesioned side as well as normal rats. Furthermore, 5-HT(1B) receptors are mainly involved in 5-HT-induced excitation while 5-HT(1A) receptors are involved in 5-HT-induced inhibition. The results suggest that 5-HT may potentiate the antiparkinsonian effect of L-DOPA through modulating the activity of globus pallidus.
Zhang
Shu-Jing
SJ
Department of Physiology, Qingdao University, Qingdao, China.
Wang
Hua
H
Xue
Yan
Y
Yung
Wing-Ho
WH
Chen
Lei
L
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D015259:Dopamine Agents / Q000494:pharmacology; D004338:Drug Combinations; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000633:toxicity; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000378:metabolism; D044302:Receptor, Serotonin, 5-HT1B / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology
D015259:Dopamine Agents; D004338:Drug Combinations; D009498:Neurotoxins; D044302:Receptor, Serotonin, 5-HT1B; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D007980:Levodopa; D016627:Oxidopamine