Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0278080 (physical dependence)
 1,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Effect of gene transfer of GLT-1, a glutamate transporter, into the locus coeruleus by recombinant adenoviruses on morphine physical dependence in rats. 1475 Sep 80

Several lines of evidence have suggested that the glutamatergic system in the nucleus accumbens (NAc) plays an important role in the conditioned rewarding effect of drugs of abuse. In addition, it is recognized that extracellular glutamate is rapidly removed from the synaptic cleft by Na+-dependent glutamate transporters in neurons and glial cells, thereby maintaining physiological levels of glutamate. We previously reported that activation of glutamate uptake by a glutamate transporter activator attenuated the acquisition of conditioned place preference induced by methamphetamine and morphine in mice. In the present study, we examined the effects of gene transfer of a glial glutamate transporter, GLT-1, into the NAc shell by recombinant adenoviruses on methamphetamine- and morphine-induced conditioned place preference in rats. Bilateral infusion of the recombinant adenoviruses into the NAc shell efficiently increased GLT-1 expression surrounding the infusion site, at least during the period 2-8 days after the infusion. In the conditioned place preference paradigm, animals were conditioned with repeated subcutaneous injections of methamphetamine (2 mg/kg) or morphine (3 mg/kg). Intra-NAc shell overexpression of GLT-1 before the conditioning significantly attenuated the conditioned place preference induced by methamphetamine or morphine, when compared with control. However, it had no effect on the somatic signs of naloxone-precipitated morphine withdrawal. These results suggest that GLT-1 within the NAc shell plays an inhibitory role in the conditioned rewarding effects of methamphetamine and morphine but not the physical dependence on morphine.
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PMID:Gene transfer of GLT-1, a glutamate transporter, into the nucleus accumbens shell attenuates methamphetamine- and morphine-induced conditioned place preference in rats. 1632 8