Varied behavioral responses induced by morphine in the tree shrew: a possible model for human opiate addiction

Abstract

Tree shrews represent a suitable animal model to study the pathogenesis of human diseases as they are phylogenetically close to primates and have a well-developed central nervous system that possesses many homologies with primates. Therefore, in our study, we investigated whether tree shrews can be used to explore the addictive behaviors induced by morphine. Firstly, to investigate the psychoactive effect of morphine on tree shrews’ behavior, the number of jumping and shuttling, which represent the vertical and horizontal locomotor activity respectively, was examined following the injection of different dosage of morphine. Our results showed intramuscular (IM) injection of morphine (5 or 10 mg/kg) significantly increased the locomotor activity of tree shrews 30–60 min post-injection. Then, using the conditioned place preference/aversion (CPP/CPA) paradigm, we found morphine-conditioned tree shrews exhibited place preference in the morphine-paired chamber on the test day. In addition, naloxone-precipitated withdrawal induced place aversion in the chronic morphine-dependent tree shrews. We evaluated the craving for morphine drinking by assessing the break point that reflects the maximum effort animals will expend to get the drug. Our data showed the break point was significantly increased when compared to the baseline on the 1st, 7th and 14th day after the abstinence. Moreover, in the intravenous morphine self-administration experiment, tree shrews conditioned with morphine responded on the active lever significantly more frequently than on the inactive lever after training. These results suggest that tree shrew may be a potential candidate for study the addictive behaviors and the underling neurological mechanisms.

Different obesity phenotypes correlated with the PI3K-AKT signaling pathway in tree shrews

“…Phagocytosis is a primary mechanism used to remove pathogens and cell debris by fusing phagosome and lysosomes to form a phagolysosome in macrophages. As expected for the 389 genes whose module membership was greater than 0.9, we observed the phagocytosis-related GO pathways, e.g., 11 'endocytosis' (Padj =0.001) and 'phagocytosis' (Padj =0.001). The most significant pathway were also phagocytosis-related.…”

Herpes Simplex Virus 1 Infection of Tree Shrews Differs from That of Mice in the Severity of Acute Infection and Viral Transcription in the Peripheral Nervous System

“…Rodent models are seldom used for chronic stress paradigms of human disease, whereas tree shrews are (43)(44)(45). Furthermore, tree shrews are finding a place in many models of human brain pathogenesis from mapping of neuropeptide distribution (46), models for opiate addiction (47) to drug target mining (48) and specific diseases such as Parkinson's disease (49). HSV infection was first reported in the tree shrew in 1978 by Darai et al, who studied the pathogenesis following intravenous, intraperitoneal, and subcutaneous infection (27).…”

Distribution of corticotropin-releasing factor in the tree shrew brain

“…Recently, many researchers have attempted to employ tree shrews as research models for a variety of human disorders (Fan et al, 2013), such as stress-related disorders Zambello et al, 2010) and human opiate addiction (Shen et al, 2014). Tree shrews have a welldeveloped visual system and color vision, so they have distinct advantages in myopia research (Abbott et al, 2011;Cao et al, 2003).…”