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  • NLG919 It is currently believed that

    2019-08-28

    It is currently believed that acute morphine administration can impair learning and memory (Friswell et al., 2008). Chronic morphine treatment can also impair access to and retention of spatial memory (Spain and Newsom, 1991, Zheng et al., 2002). Using the Morris water maze experiment, we have previously demonstrated that morphine damages spatial learning and memory ability; latency to the platform was prolonged, and the distance and time in the target quadrant, as well as the number of platform crossings, decreased. However, a D1 agonist could shorten the latency to the platform, increase the distance and time in the target quadrant, and increase the number of platform crossings (Liu et al., 2018). In the present study, we investigated the mechanisms by which the dopamine D1 receptor agonist SKF81297 alleviates morphine-induced learning and memory impairments, and how the downstream inflammatory reaction NLG919 factor, TLR4, and the learning- and memory-related factor, PKA, change. Thus, we aim to improve the understanding of how morphine leads to learning and memory disorders, which may then help to limit the occurrence of adverse reactions to morphine administration in clinical applications.
    Results
    Discussion
    Methods
    Introduction The biogenic amine dopamine (DA) is an important neurotransmitter and neuromodulator in both vertebrates and invertebrates. In insects, DA is found at a relatively high level throughout the nervous system and is the most abundant monoamine present (Donly and Caveney, 2005). DA regulates various aspects of insect behaviors such as olfactory (Selcho et al., 2009), locomotion (Draper et al., 2007), learning and forgetting (Berry et al., 2012), memory (Kruttner et al., 2015), reward (Liu et al., 2012), courtship (Keleman et al., 2012), copulation (Crickmore and Vosshall, 2013), decision-making (Zhang et al., 2007), phase change (Guo et al., 2015), and metamorphosis (Regna et al., 2016). The actions of DA have been shown to be mainly mediated via the activation of DA receptors (DARs). DARs are G protein-coupled receptors (GPCRs), belonging to class A rhodopsin-like subfamily. In vertebrates, five distinct DARs mediate all known functions of DA. They can be divided into two subfamilies based on their structural and pharmacological properties: D1-like DARs (D1 and D5), and D2-like DARs (D2, D3 and D4) (Beaulieu and Gainetdinov, 2011, Callier et al., 2003, Cardinaud et al., 1998). In invertebrates, three types of DARs were typically found and generally categorized according to the classification system applied to vertebrate DARs (Mustard et al., 2005). Members of DOP1 group of invertebrate DARs, which have been characterized in Drosophila melanogaster (Gotzes et al., 1994), Apis mellifera (Blenau et al., 1998), Bombyx mori (Ohta et al., 2009), Ixodes scapularis (Meyer et al., 2011), and Aedes aegypti (Meyer et al., 2012), are closely related to the vertebrate D1-like DARs. Members of DOP2 group, which have been characterized in D. melanogaster (Feng et al., 1996), A. mellifera (Humphries et al., 2003), B. mori (Ohta et al., 2009), I. scapularis (Meyer et al., 2011), A. aegypti (Hill et al., 2016, Meyer et al., 2012), and Periplaneta americana (Troppmann et al., 2014), are also referred to as invertebrate-type DARs (INDRs) and show more sequence similarity with D1-like DARs than D2-like DARs. Members of DOP3 group, which have been characterized in D. melanogaster (Hearn et al., 2002), A. mellifera (Beggs et al., 2005), and Tribolium castaneum (Verlinden et al., 2015), are more closely related to the NLG919 vertebrate D2-like DARs. DOP1 and DOP2 are functionally D1-like and activate adenylyl cyclase; in contrast, DOP3 are functionally D2-like and inhibit adenylyl cyclase (Mustard et al., 2005). A Drosophila GPCR that can be activated rapidly by both DA and ecdysteroids has been characterized. However, this receptor shows more structural homology to vertebrate β-adrenergic-like receptors than other DARs and will not be discussed here (Evans et al., 2014, Srivastava et al., 2005).