title: The influence of dizocilpine on the reserpine-induced behavioral and neurobiological changes in rats.
abstract: Clinical studies have demonstrated that a single dose of ketamine produces complete remission within 24h in some depression patients. The ability of ketamine to produce fast-acting antidepressant-like effects in animal models depends on rapid synthesis of brain-derived neurotrophic factor (BDNF). Here we examined effects of a single dose dizocilpine, a non-competitive NMDA receptor antagonist, on the behavioral and neurobiological changes in rats treated with a single high dose reserpine, which is a monoamine re-uptake blocker and depletes monoamines in the brain with the outcome of depression-like symptoms in animals. A single high dose reserpine (4.0mg/kg) was given to rats intraperitoneally. Forty-eight hours later, the rats showed depressive symptoms as evidenced by decreased locomotor activity in the open field and increased immobility time in the forced swim test. Meanwhile, the treatment decreased BDNF levels and neurogenesis in the hippocampus. Pretreatment of a single dose dizocilpine (0.30mg/kg), however, prevented all the reserpine-induced changes, except for GluN1 subunit. These results are suggestive of the involvement of neurogenesis and BDNF in the rapid-acting antidepressant-like behavioral effects of the NMDA receptor antagonists in the reserpinized rats.
authors.affiliation: The Mental Health Center, Shantou University Medical College, Shantou, China.
authors.forename: Zhen-Yong
authors.initials: ZY
authors.lastname: Gao
authors.affiliation: The Mental Health Center, Shantou University Medical College, Shantou, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.affiliation: The Mental Health Center, Shantou University Medical College, Shantou, China. Electronic address: huangqj@stumhc.cn.
authors.forename: Qing-Jun
authors.initials: QJ
authors.lastname: Huang
authors.affiliation: The Mental Health Center, Shantou University Medical College, Shantou, China. Electronic address: hyxu@stu.edu.cn.
authors.forename: Hai-Yun
authors.initials: HY
authors.lastname: Xu
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003863:Depression / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology; D016291:Dizocilpine Maleate / Q000494:pharmacology* / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D055495:Neurogenesis; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012110:Reserpine
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D012110:Reserpine
keywords: Antidepressant; BDNF; NMDA receptor; Neurogenesis