Morphine-Induced Dependence and Sensitization Are Altered in Mice Deficient in AMPA-Type Glutamate Receptor-A Subunits

• DOI: 10.1523/jneurosci.21-12-04451.2001
• Publication Date: 2018-04-05T02:15:54Z
• Authors: Olga Y. Vekovischeva; Daniel Zamanillo; Oxana Echenko; Timo Seppälä; Mikko Uusi-Oukari; Aapo Honkanen; Peter H. Seeburg; Rolf Sprengel; Esa R. Korpi
• Keywords: Male; Mice, Knockout; Dextroamphetamine; Behavior, Animal; Dose-Response Relationship, Drug; Morphine; Narcotic Antagonists; Brain; Drug Tolerance; Environment; Motor Activity; 3. Good health; Disease Models, Animal; Mice; 03 medical and health sciences; 0302 clinical medicine; Acute Disease; Chronic Disease; Mutagenesis, Site-Directed; Animals; Calcium; Excitatory Amino Acid Antagonists; Morphine Dependence

AMPA-type glutamate receptors have been suggested to be involved in the neurobiological mechanisms of drug addiction. We made use two mouse lines, which both modulated AMPA receptor responses. The first line is entirely deficient receptor-A (GluR-A) subunits (A−/− knock-out line) and, second one, Q582 residue GluR-A replaced by an arginine (R/R mutants), reduces calcium permeability and channel conductance containing this mutated subunit. Mice lines are healthy, but they show slightly increased locomotor activity. Acute morphine administration enhanced activity GluR-A−/− GluR-A(R/R) mice, at least as much that their wild-type littermates. Only mice did we observe reduced tolerance development tail-flick antinociception less severe naloxone-precipitated withdrawal symptoms after treatment with increasing doses, without differences plasma brain levels when compared wild type. Repeated daily sensitized responses only given measuring cages, whereas showed also repeated was home cages. Normal or even context-dependent sensitization observed amphetamine subunit-deficient mice. results indicate acute chronic effects morphine, including context-independent sensitization, subunit itself important for dependence.