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. Author manuscript; available in PMC: 2024 Dec 1.
Published in final edited form as: Psychiatry Res. 2023 Nov 3;330:115586. doi: 10.1016/j.psychres.2023.115586

Table 3:

CB2R alterations following chronic opioid exposure.

Source Species Opioid
Compound
(Route)		 Addiction Model/Exposure
Details		 CB2R outcome
measures and
method		 Results
Onaivi et al., 2008 [69] Male and Female Mice Heroin (NR) Non-cue-conditioned model.
Chronic exposure to 10 mg/kg heroin, (daily frequency and duration: NR)		 mRNA expression (RT-PCR) mRNA expression
→ Whole brain
Zhang et al., 2012 [70] Male Rats Morphine (SQ) CPP model.
Conditioning phase: 4 days of stable 10 mg/kg daily morphine injections alongside place conditioning procedure.
No morphine-unpaired group.
Animals were sacrificed the day after the injection		 mRNA expression (RT-PCR) Protein expression (Western blot)
Note: the western blot is semi-quantified, and it is not clear whether the changes are statistically significant or not.		 mRNA expression
↑ Cortex
↓ Brain stem
→ Cerebellum
Protein expression
↓ Cortex, Brain stem
→ Cerebellum
Li et.al, 2017 [67] Male Rats Morphine (SQ) CPP model.
Conditioning phase: Escalating daily dose for 4 days (5, 8, 10, and 15 mg/kg) with (morphine-paired group) and without (morphine-unpaired group) place conditioning procedure. Extinction phase: five days without morphine. Reinstatement phase: Single 5 mg/Kg morphine injection. The control group received saline injections throughout the investigation except for the reinstatement phase, in which they also received the morphine injection.
Animals were sacrificed 24 hours after each phase		 mRNA expression (RT-PCR) mRNA expression
↑ Dorsal hippocampus after conditioning phase vs. saline-treated controls.
→ Dorsal hippocampus after extinction vs. saline-treated controls and in reinstatement phases compared to saline-pretreated controls that had a single morphine injection.


Note: significant changes were observed only in the morphine-paired group but not in the morphine-unpaired group.
Zhang et.al. 2021
[57]		 Male Rats Morphine (IP) Non-cue-conditioned model.
Stable dose of 5 mg/kg, twice daily for 5 days
Animals were sacrificed one hour after the last injection.		 mRNA expression (RT-PCR) mRNA expression
↓ VTA

Abbreviation: CPP: Conditioned place preference IP: Intra-peritoneal; RT-PCR: Reverse transcriptase polymerase chain reactions; SQ: Subcutaneous; VTA: Ventral tegmental area.