Wouter Koek1. 1. Departments of Psychiatry and Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, Mail Code 7792, San Antonio, TX, 78229-3900, USA. koek@uthscsa.edu.
Abstract
RATIONALE: Given the increasing abuse of prescription opioids, particularly in adolescents, surprisingly few preclinical studies have explored effects of opioids in adolescents (versus adults). OBJECTIVES: This study compared the conditioned rewarding effects of morphine, without (experiment 1) and with morphine pre-exposure (experiment 2), in adolescent and adult male mice. METHODS: Experiment 1: On each of three consecutive days, one of the two conditioning sessions was preceded by an injection of a particular dose of morphine (0.1, 0.32, 1, 3.2, 10, 32, or 100 mg/kg, intraperitoneal) and the other by saline; place preference was tested on day 4. Experiment 2: Mice received once daily injections of saline or a particular dose of morphine (17.8 or 56 mg/kg) for 4 days, and 3 days later, place conditioning with morphine (0.32, 1, 3.2, or 10 mg/kg) began. RESULTS: In both experiments, morphine induced conditioned place preference along similar inverted U-shaped dose-response curves in adolescent and adult mice, with maximal effects between 0.32 and 10 mg/kg. Morphine pre-exposure did not sensitize morphine-induced conditioned place preference; instead, tolerance occurred, but only in adults. Adolescents were more sensitive than adults to morphine-induced locomotor stimulation. Response to novelty predicted the locomotor stimulating effects of morphine in adolescents, but not its rewarding effects. CONCLUSIONS: The rewarding effects of morphine were similar in adolescent and adult mice but showed differential tolerance after morphine pre-exposure. Adolescents were more sensitive than adults to the acute locomotor stimulating effects of morphine, consistent with dopamine systems involved in locomotor activity being overactive during adolescence.
RATIONALE: Given the increasing abuse of prescription opioids, particularly in adolescents, surprisingly few preclinical studies have explored effects of opioids in adolescents (versus adults). OBJECTIVES: This study compared the conditioned rewarding effects of morphine, without (experiment 1) and with morphine pre-exposure (experiment 2), in adolescent and adult male mice. METHODS: Experiment 1: On each of three consecutive days, one of the two conditioning sessions was preceded by an injection of a particular dose of morphine (0.1, 0.32, 1, 3.2, 10, 32, or 100 mg/kg, intraperitoneal) and the other by saline; place preference was tested on day 4. Experiment 2: Mice received once daily injections of saline or a particular dose of morphine (17.8 or 56 mg/kg) for 4 days, and 3 days later, place conditioning with morphine (0.32, 1, 3.2, or 10 mg/kg) began. RESULTS: In both experiments, morphine induced conditioned place preference along similar inverted U-shaped dose-response curves in adolescent and adult mice, with maximal effects between 0.32 and 10 mg/kg. Morphine pre-exposure did not sensitize morphine-induced conditioned place preference; instead, tolerance occurred, but only in adults. Adolescents were more sensitive than adults to morphine-induced locomotor stimulation. Response to novelty predicted the locomotor stimulating effects of morphine in adolescents, but not its rewarding effects. CONCLUSIONS: The rewarding effects of morphine were similar in adolescent and adult mice but showed differential tolerance after morphine pre-exposure. Adolescents were more sensitive than adults to the acute locomotor stimulating effects of morphine, consistent with dopamine systems involved in locomotor activity being overactive during adolescence.
Authors: L J Vanderschuren; G H Tjon; P Nestby; A H Mulder; A N Schoffelmeer; T J De Vries Journal: Psychopharmacology (Berl) Date: 1997-05 Impact factor: 4.530
Authors: Yong Zhang; Roberto Picetti; Eduardo R Butelman; Stefan D Schlussman; Ann Ho; Mary Jeanne Kreek Journal: Neuropsychopharmacology Date: 2008-09-10 Impact factor: 7.853
Authors: Nicole L Schramm-Sapyta; Q David Walker; Joseph M Caster; Edward D Levin; Cynthia M Kuhn Journal: Psychopharmacology (Berl) Date: 2009-06-23 Impact factor: 4.530
Authors: Emily Dziedowiec; Sunil U Nayak; Keenan S Gruver; Tyra Jennings; Christopher S Tallarida; Scott M Rawls Journal: Neuroscience Date: 2018-06-27 Impact factor: 3.590
Authors: Ariful Islam; Mohammad Atiqur Rahman; Megan B Brenner; Allamar Moore; Alyssa Kellmyer; Harley M Buechler; Frank DiGiorgio; Vincent R Verchio; Laura McCracken; Mousumi Sumi; Robert Hartley; Joseph R Lizza; Gustavo Moura-Letts; Bradford D Fischer; Thomas M Keck Journal: ACS Pharmacol Transl Sci Date: 2020-07-27