演題番号 : P1-p05
片山 規央 / Tadahiro Katayama:1 浄土 英一 / Eiichi Jodo:1 岡本 正博 / Masahiro Okamoto:1 鈴木 喜明 / Yoshiaki Suzuki:2 星野 研洋 / Ken-Yo Hoshino:2 香山 雪彦 / Yukihiko Kayama:1
1:公立大学法人福島県立医科大学 神経生理学講座 / Department of Neurophysiology, Fukushima Medical University School of Medicine, Fukushima, Japan 2:公立大学法人福島県立医科大学 神経精神医学講座 / Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Fukushima, Japan
Patients with schizophrenia exhibit deficits in motivation and learning, which suggests impairment in the reward system. Many studies have reported that phencyclidine (PCP) also induces schizophrenia-like negative symptoms, such as reduced motivation, blunted affect and social withdrawal in both human and animals. PCP-administered animals are therefore considered to be a reliable pharmacological model of schizophrenia. Previous studies indicated that the dopaminergic neurons in the ventral tegmental area (VTA) play a pivotal role in the development of reward-associated learning and motivation. In the present study we recorded the unit activity of VTA neurons in freely-moving rats before and after systemic administration of PCP in a classical conditioning paradigm, where intracranial stimulation to a reward area was given as an unconditioned stimulus after one of two tones (1000, 2000 Hz). After identifying the response properties of recorded neurons in the classical conditioning paradigm and social interaction, animals received an intraperitoneal injection of 10 mg/kg PCP or 1 ml/kg physiological saline. Most of VTA neurons clearly exhibited phasic excitation to both conditioned tones (CS+, CS-), though the response magnitude was much larger to the CS+. A subset of those responsive neurons also showed an increase in the spontaneous discharge rate during the social interaction. Systemic PCP considerably reduced such phasic responses to both tones, regardless of whether the spontaneous activity of neurons was affected by PCP or not. The responsiveness of neurons to CS+ recovered 180 min after PCP injection. Our present results indicate that PCP may affect firing activity of VTA neurons, which are involved in motivation, learning and social interaction. Therefore, repeated-alteration of VTA activity by chronically administered PCP may induce long-lasting changes in neural circuits to induce disturbed motivation and social interaction.