Barium potentiates the conditioned aversion to, but not the somatic signs of, morphine withdrawal in mice

Abstract Background Accumulating evidence indicates that neuroinflammation (NI) significantly contributes to drug addiction, but the conversion of NI after drug withdrawal is not clear. Here, we conducted 18F-flutriciclamide (GE180) positron emission tomography (PET) imaging to investigate the conversion of NI during drug withdrawal and conditioning-induced aversion by measuring the change in microglial activation with 18F-GE180. Methods Twelve male adult Sprague–Dawley rats were subjected to morphine withdrawal by the administration of naloxone, and six of them were used to model conditioned place aversion (CPA). 18F-GE180 PET imaging was performed for 11 rats on the last day of the morphine treatment phase and for 10 rats on the response assessment phase of the behavior conditioning procedure. A 18F-GE180 template was established for spatial normalization of each individual image, and the differential 18F-GE180 uptakes between the drug withdrawal (DW) group and the drug addiction (DA) group, the CPA group and the DA group, and the CPA group and the DW group were compared by a voxel-wise two-sample t test using SPM8. Results Both the DW group and the CPA group spent less time in the conditioning cage during the post-test phase compared with the pretest phase, but only the difference in the CPA group was significant (63.2 ± 34.6 vs. − 159.53 ± 22.02, P < 0.005). Compared with the DA group, the uptake of 18F-GE180 increased mainly in the hippocampus, visual cortex, thalamus and midbrain regions and decreased mainly in the sensory-related cortices after the administration of naloxone in both the DW and CPA groups. Increased 18F-GE180 uptake was only observed in the mesolimbic regions after conditioned aversion compared with the DW group. Conclusion In morphine-dependent rats, Neuroinflammation (NI) became more severe in the addiction-involved brain regions but remitted in the sensory-related brain regions after the administration of naloxone, and this NI induced by withdrawal was further aggravated after conditioned aversion formation thus may help to consolidate the withdrawal memory.

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FAAH inhibitor, URB-597, promotes extinction and CB1 antagonist, SR141716, inhibits extinction of conditioned aversion produced by naloxone-precipitated morphine withdrawal, but not extinction of conditioned preference produced by morphine in rats

Pharmacology Biochemistry and Behavior ◽

10.1016/j.pbb.2009.08.002 ◽

2009 ◽

Vol 94 (1) ◽

pp. 154-162 ◽

Cited By ~ 33

Author(s):

Laurie A. Manwell ◽

Elham Satvat ◽

Stefan T. Lang ◽

Craig P. Allen ◽

Francesco Leri ◽

...

Keyword(s):

Conditioned Aversion ◽

Morphine Withdrawal ◽

Conditioned Preference ◽

Cb1 Antagonist

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Alteration of Neuroinflammation Detected by 18F-GE180 PET Imaging in Place-Conditioned Rats with Morphine Withdrawal

10.21203/rs.3.rs-621858/v1 ◽

2021 ◽

Author(s):

Junpeng Li ◽

Da Shao ◽

Donglang Jiang ◽

Qi Huang ◽

Yihui Guan ◽

...

Keyword(s):

Drug Addiction ◽

Pet Imaging ◽

Drug Withdrawal ◽

Treatment Phase ◽

Response Assessment ◽

Brain Regions ◽

Conditioned Aversion ◽

Morphine Withdrawal ◽

Sprague Dawley ◽

Male Adult

Abstract Background: Accumulating evidence indicates that neuroinflammation significantly contributes to drug addiction, but the conversion of neuroinflammation after drug withdrawal is not clear. Here, we conducted 18F-flutriciclamide (GE180) positron emission tomography (PET) imaging to investigate the conversion of neuroinflammation during drug withdrawal and conditioning-induced aversion by measuring the change in microglial activation with 18F-GE180.Methods: Twelve male adult Sprague-Dawley rats were subjected to morphine withdrawal by the administration of naloxone, and six of them were used to model conditioned place aversion (CPA). 18F-GE180 PET imaging was performed for 11 rats on the last day of the morphine treatment phase and for 10 rats on the response assessment phase of the behavior conditioning procedure. A GE180 template was established for spatial normalization of each individual image, and the differential 18F-GE180 uptakes between the drug withdrawal (DW) group and the drug addiction (DA) group, the CPA group and the DA group, and the CPA group and the DW group were compared by a voxel-wise two-sample t-test using SPM8. Results: Both the DW group and the CPA group spent less time in the conditioning cage during the posttest phase compared with the pretest phase, but only the difference in the CPA group was significant (63.2 ± 34.6 vs. -159.53 ± 22.02, P < 0.005). Compared with the DA group, the uptake of 18F-GE180 increased mainly in the hippocampus, visual cortex, thalamus and midbrain regions and decreased mainly in the sensory-related cortices after the administration of naloxone in both the DW and CPA groups. Increased 18F-GE180 uptake was only observed in the mesolimbic regions after conditioned aversion compared with the DW group. Conclusion: In morphine-dependent rats, neuroinflammation became more severe in the addiction-involved brain regions but remitted in the sensory-related brain regions after the administration of naloxone, and this neuroinflammation induced by withdrawal was further aggravated after conditioned aversion formation thus may help to consolidate the withdrawal memory.

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