title: Substance P in the cerebrospinal fluid-contacting nucleus contributes to morphine physical dependence in rats.
abstract: The cerebrospinal fluid-contacting nucleus (CSF-CN), distributes and localizes in the ventral periaqueductal central gray (PAG) of the brainstem, which may influence actual composition of the cerebrospinal fluid (CSF) for non-synaptic signal transmission via releasing or absorbing bioactive substances. Many experiments have demonstrated that substance P (SP), a substance that is shown to be up-regulated in CSF-CN, plays an important role in the development of inflammatory pain and neuropathic pain. Thus in the present study, we hypothesize that SP in CSF-CN might contribute to morphine dependence in rats, inhibiting SP with (D-Pro2, D-Phe7, D-Trp9)-SP intracerebroventricular (i.c.v.) injection reduce chronic morphine dependence and withdrawal. Rats were repeatedly injected with morphine in five escalating doses for morphine physical dependence. Morphine withdrawal-like behavioral signs and morphine analgesia behaviors were monitored after naloxone administration following i.c.v. injection of (D-Pro2, D-Phe7, D-Trp9)-SP. And SP-expression of CSF-CN was evaluated with dual-label immunofluorescent technique on morphine withdrawal in rats. After i.c.v. treatment with (D-Pro2, D-Phe7, D-Trp9)-SP, the naloxone-precipitated withdrawal symptoms were significantly attenuated, paw withdrawal threshold/thermal withdrawal latency (PWT/TWL) were increased, and SP-expression in CSF-CN was significantly reduced than control group. SP, known a neurotransmitter/neuromodulator of nociception, has also been implicated in the signs of opioid withdrawal. This study provides the first evidence that SP in CSF-CN contributes to morphine physical dependence and withdrawal, which may provide an important and specific role in mediating the motivational aspects of opiates withdrawal via CSF - the parenchyma of the brain, and may represent a novel pharmacological route such as SP inhibitor i.c.v. injection for the control of drug abuse.
authors.affiliation: Department of Anesthesiology, The First Clinical College, China Medical University, Shenyang, Liaoning 110001, China. lxf0001@126.com
authors.forename: Xian-Fu
authors.initials: XF
authors.lastname: Lu
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Li
authors.forename: Chun-Guang
authors.initials: CG
authors.lastname: Wang
authors.forename: Jin-Qiu
authors.initials: JQ
authors.lastname: Wei
authors.forename: Ying
authors.initials: Y
authors.lastname: Ye
authors.forename: Li-Cai
authors.initials: LC
authors.lastname: Zhang
authors.forename: Jun-Li
authors.initials: JL
authors.lastname: Cao
mesh_terms: D000818:Animals; D005455:Fluorescent Antibody Technique; D008297:Male; D009021:Morphine Dependence / Q000378:metabolism* / Q000503:physiopathology; D010487:Periaqueductal Gray / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000378:metabolism*
chemical_list: D013373:Substance P