Repeated Morphine Produces Sensitization to Reward and Tolerance to Antiallodynia in Male and Female Rats with Chemotherapy-Induced Neuropathy

Effects of repeated treatment with methcathinone, mephedrone, and fenfluramine on intracranial self-stimulation in rats

“…(1) tolerance to ICSS depression and emergence of ICSS facilitation [e.g. with mu opioid receptor agonists like morphine (Legakis and Negus 2018;Miller et al 2015a;Reid 1987;Wiebelhaus et al 2016) or high nicotine doses (Freitas et al 2016)], (2) tolerance to ICSS depression without emergence of ICSS facilitation [e.g. with cannabinoid receptor agonists like Δ9-tetrahydrocannabinol (Grim et al 2015;Kwilasz and Negus 2012), the N-methyl-Daspartate glutamate receptor antagonist ketamine (Hillhouse et al 2014), and the delta opioid receptor agonist SNC80 (Negus et al 2012)], or (3) sustained ICSS depression [e.g.…”

Prospects for finding the mechanisms of sex differences in addiction with human and model organism genetic analysis

“…[119][120][121][122][123][124][125] Various sex differences are also observed for the other drug classes under multiple behavioral paradigms. [126][127][128][129][130] Although the magnitude and direction of the differences may vary in different species and strains, this is a "feature," not a "bug." It is precisely this variation that we are harnessing in the use of genetic variation to discover the biological mechanisms of sex differences.…”

“…For example, female rodents exhibit heightened sensitivity to psychomotor stimulant and reinforcing properties of cocaine . Various sex differences are also observed for the other drug classes under multiple behavioral paradigms …”

Role of agonist efficacy in exposure-induced enhancement of mu opioid reward in rats

“…Many drugs of abuse increase (or "facilitate") low rates of ICSS responding maintained by low frequencies or intensities of brain stimulation, and as a result, ICSS facilitation is often interpreted as an abuse-related drug effect (Negus and Miller, 2014). Morphine and other MOR agonists often fail to produce ICSS facilitation in opioid-naïve subjects, and instead produce primarily dose-dependent ICSS depression; however, repeated daily treatment over the course of several days can produce tolerance to opioid-induced ICSS depression and heightened expression of abuse-related ICSS facilitation (Altarifi et al, 2013;Legakis and Negus, 2018;Miller et al, 2015;Negus and Moerke, 2019;Reid, 1987). This trajectory of increasing opioid-induced ICSS facilitation in rats resembles the increase in opioid abuse potential that can occur during initial regimens of opioid exposure in humans.…”

“…Accordingly, the goal of this study was to compare effects on ICSS produced by repeated daily treatment with MOR agonists that ranged from low to high efficacy in stimulating MOR-coupled G-protein signaling (from lowest to highest efficacy: NAQ, nalbuphine, buprenorphine, fentanyl, methadone) (Emmerson et al, 1996;Li et al, 2009;Selley et al, 1998). All drugs were tested using an experimental design that has been used previously to show a transition from initial ICSS depression to subsequent ICSS facilitation after repeated treatment with the prototype MOR agonist morphine (Legakis and Negus, 2018;Miller et al, 2015), which has MOR agonist efficacy slightly lower than that of fentanyl (Emmerson et al, 1996;Selley et al, 1998). Morphine was also tested after repeated dosing with each test drug.…”