English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Morphine-induced dependence and sensitization are altered in mice deficient in AMPA-type glutamate receptor-A subunits

MPS-Authors
There are no MPG-Authors in the publication available
External Resource
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Vekovischeva, O., Zamanillo, D., Echenko, O., Seppala, T., Uusi-Oukari, M., Honkanen, A., et al. (2001). Morphine-induced dependence and sensitization are altered in mice deficient in AMPA-type glutamate receptor-A subunits. The Journal of Neuroscience, 21(12), 4451-4459. doi:10.1523/JNEUROSCI.21-12-04451.2001.


Cite as: https://hdl.handle.net/11858/00-001M-0000-0013-E33C-5
Abstract
AMPA-type glutamate receptors have been suggested to be involved in the neurobiological mechanisms of drug addiction. We have made use of two mouse lines, which both have modulated AMPA receptor responses. The first line is entirely deficient in glutamate receptor-A (GluR-A) subunits (A-/- knock-out line) and, in the second one, the Q582 residue of GluR-A subunits is replaced by an arginine residue (R/R mutants), which reduces the calcium permeability and channel conductance of the receptors containing this mutated subunit. Mice of both lines are healthy, but they show slightly increased locomotor activity. Acute morphine administration enhanced locomotor activity of the GluR-A-/- and GluR-A(R/R) mice, at least as much as that of their wild-type littermates. Only in the GluR-A-/- mice did we observe reduced tolerance development in tail-flick antinociception and less severe naloxone-precipitated withdrawal symptoms after treatment with increasing morphine doses, without differences in plasma and brain morphine levels when compared with wild type. Repeated daily morphine administration sensitized the locomotor activity responses in the GluR-A-/- and GluR-A(R/R) mice only when given in the measuring cages, whereas the wild-type mice showed slightly increased responses also when the repeated treatment was given in their home cages. Normal or even enhanced context-dependent sensitization was observed also with repeated amphetamine administration in the GluR-A subunit-deficient mice. The results indicate that AMPA receptors are involved in the acute and chronic effects of morphine, including context-independent sensitization, and that the GluR-A subunit itself is important for morphine tolerance and dependence.