Journal article
Sexually dimorphic activation of the periaqueductal gray–rostral ventromedial medullary circuit during the development of tolerance to morphine in the rat
The European journal of neuroscience, Vol.27(6), pp.1517-1524
03/2008
Handle:
https://hdl.handle.net/2376/114439
PMCID: PMC2821209
PMID: 18364026
Abstract
The midbrain periaqueductal gray (PAG) and its descending projections to the rostral ventromedial medulla (RVM) provides an essential neural circuit for the antinociceptive effects of opiates, and has been implicated in the development of tolerance to morphine. Systemic morphine activates a greater proportion of PAG–RVM neurons in male vs female rats, and induces tolerance to a greater degree in males. The present studies tested the hypothesis that if the PAG–RVM pathway is essential for the development of tolerance, then: (i) morphine activation of the PAG–RVM pathway should decline as tolerance develops; and (ii) sex differences in the development of tolerance to morphine should be reflected as a greater decline in the activation of this pathway in males. These hypotheses were tested in male and female rats using behavioral testing (hot-plate) and immunohistochemistry to map the activation of the PAG–RVM pathway following repeated morphine administration (5 mg/kg; s.c.). In males, morphine potency decreased from 3.0 to 6.3 mg/kg, indicating tolerance, and this was paralleled by a steady decline in the percentage of PAG–RVM output neurons activated by morphine. In contrast, in females the shift in morphine potency was significantly attenuated (D
50
6–8.3 mg/kg), and no significant difference in the activity of PAG–RVM output neurons was noted. These results demonstrate that the greater development of tolerance to morphine administration in male rats corresponds with a significant reduction in the activation of the PAG–RVM circuit and suggest a central role for the PAG in the development of tolerance to morphine.
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Details
- Title
- Sexually dimorphic activation of the periaqueductal gray–rostral ventromedial medullary circuit during the development of tolerance to morphine in the rat
- Creators
- Dayna R Loyd - Department of Biology, Center for Behavioral Neuroscience, Georgia State University, PO Box 4010, Atlanta, GA 30302-4010, USAMichael M Morgan - Department of Psychology, Washington State University, 14204 NE Salmon Creek Avenue, Vancouver, WA 98686-9600, USAAnne Z Murphy - Department of Biology, Center for Behavioral Neuroscience, Georgia State University, PO Box 4010, Atlanta, GA 30302-4010, USA
- Publication Details
- The European journal of neuroscience, Vol.27(6), pp.1517-1524
- Academic Unit
- Psychology, Department of
- Identifiers
- 99900547570701842
- Language
- English
- Resource Type
- Journal article