Role of alpha2/delta subunit in the development of morphine-induced rewarding effect and behavioral sensitization.
Previous data demonstrate that L-type voltage-gated calcium channel (VGCC) blockers, which bind to alpha(1) subunits of VGCC to suppress Ca(2+) entry into cells, inhibit the development of psychological dependence on drugs of abuse, suggesting the upregulation of L-type VGCC in the development of psychological dependence. However, there are few available data on changes of the auxiliary subunit alpha(2)/delta modifying L-type VGCC under such conditions. We therefore investigated here the role of alpha(2)/delta subunits of VGCCs in the brain of mouse after repeated treatment with morphine. The treatment with morphine increased alpha(2)/delta subunit expression in the frontal cortex and the limbic forebrain of mice showing rewarding effect and sensitization to hyperlocomotion by morphine. The morphine-induced behavioral sensitization and place preference were also suppressed by gabapentin, which binds to an exofacial epitope of the alpha(2)/delta auxiliary subunits of VGCCs. These findings indicate that the upregulation of alpha(2)/delta subunit as well as alpha(1) subunits of VGCC in the frontal cortex and the limbic forebrain plays a critical role in development of morphine-induced rewarding effect and behavioral sensitization following neuronal plasticity.
Shibasaki
M
M
Department of Pharmacology, Kawasaki Medical School, Matsushima 577, Kurashiki, Okayama 701-0192, Japan.
Kurokawa
K
K
Ohkuma
S
S
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D020746:Calcium Channels, L-Type / Q000096:biosynthesis / Q000502:physiology*; D003213:Conditioning, Psychological / Q000187:drug effects; D005625:Frontal Lobe / Q000378:metabolism; D008032:Limbic System / Q000378:metabolism; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000378:metabolism* / Q000523:psychology; D009043:Motor Activity / Q000187:drug effects; D021122:Protein Subunits / Q000096:biosynthesis / Q000502:physiology; D012201:Reward; D015854:Up-Regulation
D000701:Analgesics, Opioid; D020746:Calcium Channels, L-Type; D021122:Protein Subunits; D009020:Morphine