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GABA B receptors modulate morphine antinociception: Pharmacological and genetic approaches.
- Source :
-
Pharmacology, biochemistry, and behavior [Pharmacol Biochem Behav] 2019 May; Vol. 180, pp. 11-21. Date of Electronic Publication: 2019 Mar 06. - Publication Year :
- 2019
-
Abstract
- Previous studies in our laboratory showed an interaction between the GABAergic and opioid systems involved in the analgesic effect of baclofen (BAC). Furthermore, it is known that sex differences exist regarding various pharmacological responses of morphine (MOR) and they are related to an increased sensitivity to MOR effects in males. The aims of the present study were to evaluate the possible involvement of the GABA <subscript>B</subscript> receptors in the antinociceptive responses induced by MOR (1, 3 and 9 mg/kg, s.c.) administration using both pharmacological (BAC 2 mg/kg, i.p.; and 2-OH-saclofen, SAC 0.3 mg/kg, intra cisterna magna) and genetic approaches (GABA <subscript>B1</subscript> knockout mice; GABA <subscript>B1</subscript> KO) in mice of both sexes. In addition, we explored the alterations in c-Fos expression of different brain areas involved in the antinociceptive effect of MOR using both approaches. The pharmacological approach showed a higher dose-dependent antinociceptive effect of MOR in male mice compared to female mice. BAC and SAC pretreatment potentiated and attenuated the antinociceptive effect of MOR, respectively, in both sexes. The genetic approach revealed a dose-dependent antinociceptive effect of MOR in the wild type mice, but not in the GABA <subscript>B1</subscript> KO mice and no sex differences were observed. Additionally, BAC and SAC pretreatment and the lack of GABA <subscript>B1</subscript> subunit of the GABA <subscript>B</subscript> receptor prevented the changes observed in c-Fos expression in the cingulate cortex and nucleus accumbens of male mice. Our results suggest that the GABA <subscript>B</subscript> receptors are involved in the MOR antinociceptive effect of both male and female mice.<br /> (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Subjects :
- Analgesics administration & dosage
Animals
Baclofen administration & dosage
Baclofen analogs & derivatives
Baclofen pharmacology
Behavior, Animal drug effects
Dose-Response Relationship, Drug
Female
GABA-B Receptor Agonists administration & dosage
GABA-B Receptor Agonists pharmacology
Gene Knockout Techniques
Genes, fos genetics
Genotype
Gyrus Cinguli drug effects
Gyrus Cinguli metabolism
Locomotion drug effects
Male
Mice
Mice, Inbred BALB C
Mice, Knockout
Morphine administration & dosage
Nucleus Accumbens drug effects
Nucleus Accumbens metabolism
Proto-Oncogene Proteins c-fos immunology
Proto-Oncogene Proteins c-fos metabolism
Sex Factors
Signal Transduction drug effects
Analgesics pharmacology
Morphine pharmacology
Receptors, GABA-B genetics
Receptors, GABA-B metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1873-5177
- Volume :
- 180
- Database :
- MEDLINE
- Journal :
- Pharmacology, biochemistry, and behavior
- Publication Type :
- Academic Journal
- Accession number :
- 30851293
- Full Text :
- https://doi.org/10.1016/j.pbb.2019.02.015