title: CCL5 and cytokine expression in the rat brain: differential modulation by chronic morphine and morphine withdrawal.
abstract: Opioids have been shown to influence the immune system and to promote the expression of pro-inflammatory cytokines in the central nervous system. However, recent data have shown that activation of opioid receptors increases the expression and release of the neuroprotective chemokine CCL5 from astrocytes in vitro. To further define the interaction between CCL5 and inflammation in response to opioids, we have examined the effect of chronic morphine and morphine withdrawal on the in vivo expression of CCL5 as well as of pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Rats undergoing a chronic morphine paradigm (10 mg/kg increasing to 30 mg/kg, twice a day for 5 days) showed a twofold increase of CCL5 protein and mRNA within the cortex and striatum. No changes were observed in the levels of IL-1β and TNF-α. Naltrexone blocked the effect of morphine. A chronic morphine paradigm with no escalating doses (10 mg/kg, twice a day) did not alter CCL5 levels compared to saline-treated animals. On the contrary, rats undergoing spontaneous morphine withdrawal exhibited lower levels of CCL5 within the cortex as well as increased levels of pro-inflammatory cytokines and Iba-1 positive cells than saline-treated rats. Overall, these data suggest that morphine withdrawal may promote cytokines and other inflammatory responses that have the potential of exacerbating neuronal damage.
authors: Department of Pharmacology and Physiology, Laboratory of Preclinical Neurobiology Georgetown University Medical Center, Washington DC 20057, United States.
authors: Lee A
authors: LA
authors: Campbell
authors: Valeriya
authors: V
authors: Avdoshina
authors: Summer
authors: S
authors: Rozzi
authors: Italo
authors: I
authors: Mocchetti
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced*; D008297:Male; D017628:Microglia / Q000378:metabolism; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome
chemical_list: D018946:Chemokine CCL5; D016207:Cytokines; D009020:Morphine
keywords: CCL5; Frontal cortex; IL-1β; Microglia; Morphine dependence; Morphine withdrawal; Naltrexone; Striatum
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