Yutaka Gomita1, Satoru Esumi2, Yoshihisa Kitamura2, Hirotoshi Motoda3, Toshiaki Sendo2, Hidenori Sagara4, Hiroaki Araki5, Mitsunobu Mio6, Shigeki Inoue3, Yoshio Kano3. 1. Department of Pharmacy, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan. Electronic address: pnh78qrk@okayama-u.ac.jp. 2. Department of Pharmacy, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan. 3. Graduate School of Health of Science, Kibi International University, 8 Iga-machi Takahashi City, Okayama 716-8508, Japan. 4. Center for Clinical Pharmacy, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-295, Japan. 5. Division of Pharmacy, Ehime University Hospital, Shitsukawa, Toon, Ehime 791-0295, Japan. 6. School of Pharmacy, Shujitsu University, 1-6-1 Nishigawara, Naka-ku, Okayama 703-8516, Japan.
Abstract
AIM: In mammals, rewarding and aversive states are motivational drivers of behavioral expression. However, it is unclear whether such states affect neuronal functions at the level of individual neurons. In the present study, the neuronal effects of rewarding and aversive states were investigated in using PC12 mutant cells (PC12m3 cells) with low sensitivity to nerve growth factor. MAIN METHODS: The intracranial self-stimulation (ICSS) and immobilization (IMM) methods were used to create rewarding and aversive states, respectively, in rats. Furthermore, experiments involving voluntary running on a wheel and forced running on a rotating rod were used to evaluate the effects of behavioral excitement on neurons. Then, the effects of plasma samples collected from the animals on neurite extension were examined microscopically, and p38 mitogen-activated protein kinase (MAPK) activity was assessed using Western blotting. KEY FINDINGS: Plasma samples from the ICSS and IMM rats facilitated neurite outgrowth to different degrees. However, their effects were not influenced by behavioral excitement. Furthermore, the plasma from the ICSS rats also induced upregulated p38 MAPK activity, whereas that from the IMM rats produced the same or slightly lower levels of MAPK activity to the control plasma. SIGNIFICANCE: These findings indicate that rewarding and aversive states might cause morphological changes, such as neurite extension. As for the effects of these states on p38 MAPK activity, the former state might directly increase p38 MAPK activity, but the latter state might have no effect or cause a slight reduction in p38 MAPK activity.
AIM: In mammals, rewarding and aversive states are motivational drivers of behavioral expression. However, it is unclear whether such states affect neuronal functions at the level of individual neurons. In the present study, the neuronal effects of rewarding and aversive states were investigated in using PC12 mutant cells (PC12m3 cells) with low sensitivity to nerve growth factor. MAIN METHODS: The intracranial self-stimulation (ICSS) and immobilization (IMM) methods were used to create rewarding and aversive states, respectively, in rats. Furthermore, experiments involving voluntary running on a wheel and forced running on a rotating rod were used to evaluate the effects of behavioral excitement on neurons. Then, the effects of plasma samples collected from the animals on neurite extension were examined microscopically, and p38 mitogen-activated protein kinase (MAPK) activity was assessed using Western blotting. KEY FINDINGS: Plasma samples from the ICSS and IMM rats facilitated neurite outgrowth to different degrees. However, their effects were not influenced by behavioral excitement. Furthermore, the plasma from the ICSS rats also induced upregulated p38 MAPK activity, whereas that from the IMM rats produced the same or slightly lower levels of MAPK activity to the control plasma. SIGNIFICANCE: These findings indicate that rewarding and aversive states might cause morphological changes, such as neurite extension. As for the effects of these states on p38 MAPK activity, the former state might directly increase p38 MAPK activity, but the latter state might have no effect or cause a slight reduction in p38 MAPK activity.