The interaction of morphine and gamma-aminobutyric acid (GABA)ergic systems in anxiolytic behavior: using mu-opioid receptor knockout mice.
We investigated the interaction of morphine and gamma-aminobutyric acid (GABA)ergic systems in anxiolytic action using mu-opioid receptor knockout and wild-type female mice. An elevated plus-maze test was used to assess anxiolytic behavior. The anxiolytic activities were monitored after experimental animals were pretreated with morphine [15 mg/kg, subcutaneous (s.c.)] and 3 h later received a single dose of muscimol (0.5 mg/kg, s.c.). In another experiment, mice received a single dose of opioid antagonist, naloxone [1.0 mg/kg, intraperitoneal (i.p.)], or GABA(A) receptor antagonist, (+)bicucullin (2.0 mg/kg, i.p.), 2.5 h after the morphine and 30 min before the muscimol injection. Control mice received vehicle only. The results show that morphine enhanced muscimol-induced staying time in open arms by 160% in wild-type mice. Moreover, the effect of morphine in the wild type was inhibited by the pretreatment of either naloxone or (+)bicucullin. Autoradiographic analysis indicated that morphine-administration raised [(3)H]muscimol binding by around 25% of the basal level in posterior thalamic, mediodorsal thalamic, and amygdaloid areas, but not in the hippocampal area in wild-type mice. In contrast, morphine administration did not alter the [(3)H]muscimol binding in mu-opioid receptor knockout mice. The present results reveal that mu-opioid receptor may play a role in the modification of anxiolytic behavior regulated by GABAergic neurotransmission.
Sasaki
Kenroh
K
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, USA.
Fan
Lir Wan
LW
Tien
Lu Tai
LT
Ma
Tangeng
T
Loh
Horace H
HH
Ho
Ing K
IK
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D030762:Estrous Cycle / Q000502:physiology; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology*; D009118:Muscimol / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000172:deficiency* / Q000235:genetics; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D004967:Estrogens; D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D009292:Narcotic Antagonists; D011963:Receptors, GABA-A; D017450:Receptors, Opioid, mu; D009118:Muscimol; D009270:Naloxone; D005680:gamma-Aminobutyric Acid; D009020:Morphine