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Dose\u2010addition analyses provide a rigorous and quantitative method to determine the nature of the interaction (i.e., supraadditive, additive, or subadditive) between two or more drugs. As briefly reviewed here, studies in rhesus monkeys have applied dose\u2010addition analyses to group level data to characterize the nature of the interaction between the reinforcing effects of stimulants and opioids (e.g., mixtures of cocaine + heroin). Building upon these foundational studies, more recent work has applied dose\u2010addition analyses to better understand the nature of the interaction between caffeine and illicit stimulants such as MDPV and methamphetamine in rats. In\u00a0addition to utilizing a variety of operant procedures, including drug discrimination, drug self\u2010administration, and drug\u2010primed reinstatement, these studies have incorporated potency and effectiveness ratios as a method for both statistical analysis and visualization of departures from additivity at both the group and individual subject level. As such, dose\u2010addition analyses represent a powerful and underutilized approach to quantify the nature of drug\u2013drug interactions that can be applied to a variety of abuse\u2010related endpoints in order to better understand the behavioral pharmacology of polysubstance use.<\/jats:p>","DOI":"10.1002\/jeab.741","type":"journal-article","created":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T08:23:32Z","timestamp":1644481412000},"page":"442-456","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Application of dose\u2010addition analyses to characterize the abuse\u2010related effects of drug mixtures"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4303-2478","authenticated-orcid":false,"given":"Michelle R","family":"Doyle","sequence":"first","affiliation":[{"name":"Department of Pharmacology University of Texas Health Science Center at San Antonio"},{"name":"South Texas Veterans Health Care System  San Antonio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1428-2400","authenticated-orcid":false,"given":"Brenda M","family":"Gannon","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Texas Health Science Center at San Antonio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melson P","family":"Mesmin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Texas Health Science Center at San Antonio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2499-3356","authenticated-orcid":false,"given":"Gregory T","family":"Collins","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Texas Health Science Center at San Antonio"},{"name":"South Texas Veterans Health Care System  San Antonio"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,10]]},"reference":[{"key":"e_1_2_3_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2013.04.003"},{"key":"e_1_2_3_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.FORSCIINT.2021.110911"},{"key":"e_1_2_3_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/S12889-021-11757-X"},{"key":"e_1_2_3_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/DTA.155"},{"key":"e_1_2_3_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-3057(98)00041-0"},{"key":"e_1_2_3_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.FORSCIINT.2015.09.014"},{"key":"e_1_2_3_8_1","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.2019.305412"},{"key":"e_1_2_3_9_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.116.234252"},{"key":"e_1_2_3_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-019-05339-4"},{"key":"e_1_2_3_11_1","doi-asserted-by":"publisher","DOI":"10.1037\/PHA0000209"},{"key":"e_1_2_3_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00426372"},{"key":"e_1_2_3_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02247378"},{"key":"e_1_2_3_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-020-00949-3"},{"key":"e_1_2_3_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/FNINS.2020.00569"},{"key":"e_1_2_3_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/hcq056"},{"key":"e_1_2_3_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2021.173112"},{"key":"e_1_2_3_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12904"},{"key":"e_1_2_3_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-3057(98)00098-7"},{"key":"e_1_2_3_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/1556-4029.13968"},{"key":"e_1_2_3_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/S00213-010-2131-1"},{"key":"e_1_2_3_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-018-0209-3"},{"key":"e_1_2_3_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2017.141"},{"key":"e_1_2_3_24_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.116.239376"},{"key":"e_1_2_3_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-018-5046-x"},{"key":"e_1_2_3_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2019.04.024"},{"key":"e_1_2_3_27_1","doi-asserted-by":"publisher","DOI":"10.1366\/000370208784658002"},{"key":"e_1_2_3_28_1","doi-asserted-by":"publisher","DOI":"10.7326\/M17-0865"},{"key":"e_1_2_3_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(89)90075-0"},{"key":"e_1_2_3_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2019.01.031"},{"issue":"1","key":"e_1_2_3_31_1","first-page":"274","article-title":"Synergistic elevations in nucleus accumbens extracellular dopamine concentrations during self\u2010administration of cocaine\/heroin combinations (speedball) in rats","volume":"288","author":"Hemby S. 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