Effects of phencyclidine on behavior and extracellular levels of dopamine and its metabolites in neonatal ventral hippocampal damaged rats

Kozo Kato, Toshiaki Shishido, Masami Ono, Kyoko Shishido, Masanori Kobayashi, Hiroki Suzuki, Toshitaka Nabeshima, Hiroshi Furukawa, Shin ich Niwa

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22 Citations (Scopus)

Abstract

Rationale: The use of neonatal hippocampal lesioned rats is well established in animal models of schizophrenia. Moreover, the dysfunction of N-methyl-D-aspartate (NMDA) neurotransmission may play a crucial role in the pathophysiology of schizophrenia. Objective: To examine the role of NMDA neurotransmission in the neonatal ventral hippocampal damaged rat. Methods: In initial experiments, we compared the effects of mild environmental stress (HAB) and the injection of saline and methamphetamine (MAP, 1.5 mg/kg, IP) in lesioned and sham-operated rats. We also examined the effects of a single injection of phencyclidine (PCP, 10 mg/kg, IP) on locomotor activity and extracellular levels of dopamine (DA) and its metabolites in the nucleus accumbens (NAc) of lesioned and sham-operated rats using an in vivo brain microdialysis method. Results: Compared with sham-operated controls, the lesioned rats showed increased locomotor activity at postnatal day 56 (PD56) but not at PD35 after HAB and MAP administration. Similarly, the lesioned rats showed increased locomotor activity at PD56 but not at PD35 after PCP administration. Unexpectedly, the increase in DA levels was significantly greater in the sham-operated rats than in the lesioned rats. Conclusions: The results suggest that neonatal hippocampal lesioned rats are accompanied by the dysfunction of NMDA neurotransmission. They also suggest that hyperresponsiveness to PCP following neonatal hippocampal lesions does not depend on the extracellular DA concentration in the NAc.

Original languageEnglish
Pages (from-to)163-169
Number of pages7
JournalPsychopharmacology
Volume150
Issue number2
DOIs
Publication statusPublished - 15-07-2000

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Phencyclidine
Dopamine
N-Methylaspartate
Locomotion
Synaptic Transmission
Nucleus Accumbens
Schizophrenia
Injections
Methamphetamine
Microdialysis
Animal Models

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Kato, Kozo ; Shishido, Toshiaki ; Ono, Masami ; Shishido, Kyoko ; Kobayashi, Masanori ; Suzuki, Hiroki ; Nabeshima, Toshitaka ; Furukawa, Hiroshi ; Niwa, Shin ich. / Effects of phencyclidine on behavior and extracellular levels of dopamine and its metabolites in neonatal ventral hippocampal damaged rats. In: Psychopharmacology. 2000 ; Vol. 150, No. 2. pp. 163-169.
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Effects of phencyclidine on behavior and extracellular levels of dopamine and its metabolites in neonatal ventral hippocampal damaged rats. / Kato, Kozo; Shishido, Toshiaki; Ono, Masami; Shishido, Kyoko; Kobayashi, Masanori; Suzuki, Hiroki; Nabeshima, Toshitaka; Furukawa, Hiroshi; Niwa, Shin ich.

In: Psychopharmacology, Vol. 150, No. 2, 15.07.2000, p. 163-169.

Research output: Contribution to journalArticle

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AU - Kato, Kozo

AU - Shishido, Toshiaki

AU - Ono, Masami

AU - Shishido, Kyoko

AU - Kobayashi, Masanori

AU - Suzuki, Hiroki

AU - Nabeshima, Toshitaka

AU - Furukawa, Hiroshi

AU - Niwa, Shin ich

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N2 - Rationale: The use of neonatal hippocampal lesioned rats is well established in animal models of schizophrenia. Moreover, the dysfunction of N-methyl-D-aspartate (NMDA) neurotransmission may play a crucial role in the pathophysiology of schizophrenia. Objective: To examine the role of NMDA neurotransmission in the neonatal ventral hippocampal damaged rat. Methods: In initial experiments, we compared the effects of mild environmental stress (HAB) and the injection of saline and methamphetamine (MAP, 1.5 mg/kg, IP) in lesioned and sham-operated rats. We also examined the effects of a single injection of phencyclidine (PCP, 10 mg/kg, IP) on locomotor activity and extracellular levels of dopamine (DA) and its metabolites in the nucleus accumbens (NAc) of lesioned and sham-operated rats using an in vivo brain microdialysis method. Results: Compared with sham-operated controls, the lesioned rats showed increased locomotor activity at postnatal day 56 (PD56) but not at PD35 after HAB and MAP administration. Similarly, the lesioned rats showed increased locomotor activity at PD56 but not at PD35 after PCP administration. Unexpectedly, the increase in DA levels was significantly greater in the sham-operated rats than in the lesioned rats. Conclusions: The results suggest that neonatal hippocampal lesioned rats are accompanied by the dysfunction of NMDA neurotransmission. They also suggest that hyperresponsiveness to PCP following neonatal hippocampal lesions does not depend on the extracellular DA concentration in the NAc.

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