Effect of gene transfer of GLT-1, a glutamate transporter, into the locus coeruleus by recombinant adenoviruses on morphine physical dependence in rats.
There is a body of evidence implying the involvement of the central glutamatergic system in morphine dependence. We previously reported changes in the mRNA expression of a glial glutamate transporter GLT-1 in some brain regions of morphine-dependent and naloxone-precipitated withdrawal rats, and inhibition of morphine physical dependence by a glutamate transporter activator in mice. These findings support the possibility that glutamate transporters such as GLT-1 are involved in morphine dependence. In this study, we examined the effects of gene transfer of GLT-1 into the locus coeruleus (LC) by recombinant adenoviruses on morphine physical dependence in rats. We constructed recombinant adenoviruses that successfully delivered the GLT-1 gene in vitro and in vivo. Local overexpression of GLT-1 within the bilateral LC by the recombinant adenoviruses before implantation of the morphine pellet significantly inhibited various somatic signs of naloxone-precipitated morphine withdrawal, compared with the control. These results suggest that GLT-1 within the LC plays an inhibitory role in morphine physical dependence.
Ozawa
Tohru
T
Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
Nakagawa
Takayuki
T
Sekiya
Yumiko
Y
Minami
Masabumi
M
Satoh
Masamichi
M
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D018698:Glutamic Acid / Q000378:metabolism*; D008125:Locus Coeruleus / Q000187:drug effects* / Q000378:metabolism*; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009433:Neural Inhibition / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000235:genetics; D009435:Synaptic Transmission / Q000235:genetics
D027342:Excitatory Amino Acid Transporter 2; D009292:Narcotic Antagonists; D011993:Recombinant Fusion Proteins; D018698:Glutamic Acid; D009020:Morphine