title: Effects of an oxycodone conjugate vaccine on oxycodone self-administration and oxycodone-induced brain gene expression in rats.
abstract: Prescription opioid abuse is an increasing public health concern in the USA. A vaccine comprising a hapten (OXY) conjugated to the carrier protein keyhole limpet hemocyanin (OXY-KLH) has been shown to attenuate the antinociceptive effects of oxycodone. Here, the vaccine's ability to prevent acquisition of intravenous (i.v.) oxycodone self-administration was studied in rats. Effects of vaccination on oxycodone-induced changes in the expression of several genes within the mesolimbic system, which are regulated by chronic opiate use, were also examined. Vaccination with OXY-KLH reduced the proportion of rats acquiring i.v. self-administration of oxycodone under a fixed ratio (FR) 3 schedule of reinforcement compared to control rats immunized with the unconjugated KLH carrier protein. Vaccination significantly reduced the mean number of infusions at FR3, total number of infusions, and total oxycodone intake during the entire protocol. Compared to oxycodone self-administering control rats immunized with the carrier alone, rats vaccinated with the OXY-KLH immunogen showed increased levels of adenylate cyclase 5 (Adcy5) and decreased levels of early growth response protein 2 (Egr2) and the early immediate gene c-Fos in the striatum. These data suggest that vaccination with OXY-KLH can attenuate the reinforcing effects of oxycodone at a clinically-relevant exposure level. Analysis of mRNA expression identified some addiction-relevant markers that may be of interest in understanding oxycodone effects or the protection provided by vaccination.
authors.affiliation: Minneapolis Medical Research Foundation, Minneapolis, Minnesota, United States of America; University of Minnesota, School of Medicine, Department of Medicine, Minneapolis, Minnesota, United States of America; University of Minnesota, School of Medicine, Department of Pharmacology, Minneapolis, Minnesota, United States of America.
authors.forename: Marco
authors.initials: M
authors.lastname: Pravetoni
authors.affiliation: Minneapolis Medical Research Foundation, Minneapolis, Minnesota, United States of America; University of Minnesota, School of Medicine, Department of Medicine, Minneapolis, Minnesota, United States of America; University of Minnesota, School of Medicine, Department of Pharmacology, Minneapolis, Minnesota, United States of America.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Pentel
authors.affiliation: Harvard Medical School, Department of Psychiatry, McLean Hospital, Belmont, Massachusetts, United States of America.
authors.forename: David N
authors.initials: DN
authors.lastname: Potter
authors.affiliation: Harvard Medical School, Department of Psychiatry, McLean Hospital, Belmont, Massachusetts, United States of America.
authors.forename: Elena H
authors.initials: EH
authors.lastname: Chartoff
authors.affiliation: Minneapolis Medical Research Foundation, Minneapolis, Minnesota, United States of America.
authors.forename: Laura
authors.initials: L
authors.lastname: Tally
authors.affiliation: Minneapolis Medical Research Foundation, Minneapolis, Minnesota, United States of America.
authors.forename: Mark G
authors.initials: MG
authors.lastname: LeSage
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D001921:Brain / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006241:Haptens / Q000276:immunology; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008297:Male; D009293:Opioid-Related Disorders / Q000517:prevention & control; D010098:Oxycodone / Q000008:administration & dosage* / Q000276:immunology*; D051381:Rats; D012646:Self Administration; D018074:Vaccines, Conjugate / Q000276:immunology*
chemical_list: D000701:Analgesics, Opioid; D006241:Haptens; D007074:Immunoglobulin G; D018074:Vaccines, Conjugate; D010098:Oxycodone