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.
Highlights
Preclinical studies involving animal behavior have been pivotal for providing insights into the psychobiological substrates of drug addiction, the understanding and knowledge of which increase in parallel with the refinement of animal models of this pathology
To our knowledge, our study was the first to demonstrate that tree shrews can be used for studying the effects of addictive drugs, such as morphine, on behavior using the conditioned place preference (CPP)/CPA and selfadministration paradigms
Our present data showed that the first two injections of three doses of morphine resulted in significant increases in the vertical and horizontal activity 30–120 min post-injection, and the peak effect occurred during the second hour of 10 mg/kg morphine injection
Summary
Preclinical studies involving animal behavior have been pivotal for providing insights into the psychobiological substrates of drug addiction, the understanding and knowledge of which increase in parallel with the refinement of animal models of this pathology. Rodents (mainly rats and mice) are popular animal models for drug addiction research because of their small size, rapid propagation, the availability of a variety of inbred strains, and transgenic techniques. There are some differences between rodent species and humans in terms of genetics, pathology, and pharmacology. These differences make it difficult to translate data to the human paradigm and have limited application in further studies on this topic. A recent whole genome sequencing study confirms that the Chinese tree shrew has a closer affinity to nonhuman primates than rodents, indicating they may be more suitable for the study of the pathogenesis of human disease (Fan et al, 2013). Present studies indicate that the neurochemical characterization of the tree shrew striatum, especially dorsal striatum (Rice et al, 2011) and nucleus accumbens (McCollum and Roberts, 2014), more closely resembles that of the primate than the rodent
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