title: Individual differences in initial morphine sensitivity as a predictor for the development of opiate addiction in rats.
abstract: Individuals report a wide range of analgesia to similar doses of opiates, and not all opiate users become addicted. This suggests that there may be certain predispositions that influence one to develop opiate addiction. We investigated the relationship between the individual differences in initial morphine sensitivity and the subsequent development of opiate addiction-like behavior using a hot plate test and an intravenous morphine self-administration (MSA) paradigm in rats. Using a median split of initial morphine antinociception, animals were defined as low antinociception (LA) and high antinociception (HA) groups. Thus, the LA group represents the animals that were less sensitive to initial morphine antinociception as compared to those of the HA group. The animals were allowed to self-administer either saline or morphine (0.5mg/kg/infusion, 4hr/day) 5days per week for 3 weeks. Spontaneous locomotor activity was measured on self-administration days 10 and 15. Individual differences in initial morphine sensitivity were not correlated with the amount of morphine self-administered by the animals on day 1. In the second-week of MSA, the LA group exhibited increased morphine intake and locomotor hyperactivity as compared to those of the HA group. Therefore, certain animals that are less sensitive to initial morphine antinociception may be susceptible to developing opiate addiction. The current findings may have clinical implications for future research on the biological mechanisms of opiate addiction and preclinical medication development.
authors.affiliation: Center for the Study of Traumatic Stress, 4301 Jones Bridge Road, Bethesda, MD 20814, USA; Department of Psychiatry, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Nishida
authors.affiliation: Center for the Study of Traumatic Stress, 4301 Jones Bridge Road, Bethesda, MD 20814, USA; Department of Psychiatry, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
authors.forename: Thomas Y
authors.initials: TY
authors.lastname: Park
authors.affiliation: Department of Psychiatry, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA; Department of Acupuncture, Moxibustion and Acupoint, College of Korean Medicine, Daegu Haany University, South Korea.
authors.forename: Bong Hyo
authors.initials: BH
authors.lastname: Lee
authors.affiliation: Center for the Study of Traumatic Stress, 4301 Jones Bridge Road, Bethesda, MD 20814, USA; Department of Psychiatry, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA; Program in Neuroscience, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Ursano
authors.affiliation: Center for the Study of Traumatic Stress, 4301 Jones Bridge Road, Bethesda, MD 20814, USA; Department of Psychiatry, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA; Program in Neuroscience, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. Electronic address: kwang.choi@usuhs.edu.
authors.forename: Kwang H
authors.initials: KH
authors.lastname: Choi
mesh_terms: D000698:Analgesia / Q000379:methods; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance / Q000502:physiology*; D007206:Individuality; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009293:Opioid-Related Disorders / Q000503:physiopathology; D010146:Pain / Q000188:drug therapy; D017207:Rats, Sprague-Dawley; D012646:Self Administration / Q000379:methods
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine
keywords: Drug self-administration; Locomotor activity; Morphine; Opiate addiction; Opioid analgesia; Pain