Intracranial self-stimulation-reward or immobilization-aversion had different effects on neurite extension and the ERK pathway in neurotransmitter-sensitive mutant PC12 cells.
Various actions trigger pleasure (reward) or aversion (punishment) as emotional responses. Emotional factors that negatively affect brain neural control processes for long periods of time might cause various mental diseases by inducing neuronal changes. In the present study, newly developed PC12m12 cells which are　highly sensitivity to neurotransmitters such as acetylcholine (ACh), were used. Exposing the cells to plasma from rats that had been subjected to intracranial self-stimulation (ICSS) markedly upregulated neurite outgrowth. In addition, voluntary running in a wheel or forced on a rotating rod was used to induce behavioral excitation in rats, and examinations of their plasma confirmed that the ICSS-induced neurite outgrowth was not associated with the ICSS behavior itself. Furthermore, immunoblotting and treatment with U0126, an ERK (extracellular signal-regulated kinase) antagonist, showed that the ICSS-induced neurite outgrowth was related to neuronal ERK activity. Exposing the same cells to plasma from rats that had been subjected to immobilization (IMM) also increased neurite outgrowth. Although the degree of enhancement was not as great as that seen after the ICSS rat plasma treatment, it was less than that observed after treatment with ACh as a positive control. These results indicate that ICSS or IMM lead to varying degrees of morphological changes, such as enhanced neurite outgrowth, in PC12m12 cells, but the neuronal signal transduction pathways underlying these effects differ; i.e.,the former morphological change might involve the activation of the ERK pathway, whereas the latter changes might not. Using PC12m12 cells which exhibit sensitivity to neurotransmitters, it might be possible to clarify the pathogeneses of mental diseases at the neuronal level and search for therapeutic drugs.
['Gomita|Yutaka|Y|', 'Esumi|Satoru|S|', 'Ushio|Soichiro|S|', 'Kitamura|Yoshihisa|Y|', 'Sendo|Toshiaki|T|', 'Motoda|Hirotoshi|H|', 'Inoue|Shigeki|S|', 'Araki|Hiroaki|H|', 'Kano|Yoshio|Y|']
D000818:Animals D001522:Behavior, Animal D002070:Butadienes D004644:Emotions D004791:Enzyme Inhibitors D048049:Extracellular Signal-Regulated MAP Kinases D020935:MAP Kinase Signaling System D008297:Male D020932:Nerve Growth Factor D016501:Neurites D055495:Neurogenesis D009570:Nitriles D016716:PC12 Cells D057181:Pleasure D051381:Rats D017208:Rats, Wistar D012201:Reward
Neurotransmitters Plasma Intracranial self-stimulation reward Neurite-outgrowth PC12 mutant cells Restrict immobilization aversion