Summary
We had previously demonstrated that opioid receptors contribute to the induction and expression of behavioral sensitization induced by repeated daily injection with 2.5 mg/kg of methamphetamine for 7 days. Using the same regimen, the present study investigated the alterations in μ-opioid receptor during the induction (on days 2, 5, and 8) and expression (on days 11 and 21) periods of behavioral sensitization. Radioligand binding revealed that the maximal binding of μ-opioid receptor was not changed on days 2 and 5, but down-regulated on day 8. After cessation of drug treatment, the maximal binding of μ-opioid receptor gradually and time-dependently returned to normal level on day 11 and up-regulated on day 21. In contrast, no changes in δ- and κ-opioid receptors were detectable on any given day examined. The potency of DAMGO for [35S]-GTPγS coupling was enhanced on days 2, 5, 11, and 21. Moreover, 1 μM of naltrexone or β-chlornaltrexamine significantly suppressed the basal [35S]-GTPγS coupling on days 2, 11, and 21. These findings indicate enhanced responsiveness and elevated constitutive activity of μ-opioid receptor. In summary, our data clearly demonstrate that alterations in μ-opioid receptor are involved in and may contribute to the sensitization to locomotor stimulating effect of methamphetamine.
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Abbreviations
- ANOVA:
-
analysis of variance
- AMPH:
-
amphetamine
- β-CNA:
-
β-chlornaltrexamine
- DAMGO:
-
[d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin
- DPDPE:
-
[d-Pen2,5]-enkephalin
- GDP:
-
guanosine 5′-diphosphate
- [35S]-GTPγS:
-
guanosine 5′-O-(3-[35S]-thio) triphosphate
- METH:
-
methamphetamine
- NAcc:
-
nucleus accumbens
- NAT:
-
naltrexone
- U69,593:
-
( + )-(5α,7α,8β)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]-benzeneacetamide
- VTA:
-
ventral tegmental area
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Acknowledgements
This study was supported by research funds received from the Center of Psychiatric Neuroscience at the University of Mississippi Medical Center which is supported by NIH Grant Number P20 RR0l7701.
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Chiu, CT., Ma, T. & Ho, I.K. Methamphetamine-induced behavioral sensitization in mice: alterations in μ-opioid receptor. J Biomed Sci 13, 797–811 (2006). https://doi.org/10.1007/s11373-006-9102-x
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DOI: https://doi.org/10.1007/s11373-006-9102-x