Morphine - the main pillar of nociceptive pain management - systemic use is associated
with development of tolerance and dependence. Tolerance and dependence lay a heavy burden
in clinical pain management settings. An added weight to this dilemma is that effective, safe,
and tolerable solution to this problem is still beyond reach. Antidepressants were reported as
possible alleviators of opioid tolerance and dependence. One of the increasingly used
antidepressant in clinical practice is bupropion given its high safety and tolerability profile.
Methods
The study was performed on male Balb-c mice weighing 20-30 grams. Hot plate test was
used for assessment of bupropion (5 mg/kg, ip) possible analgesic activity and enhancement of
morphine acute analgesia (1 and 5 mg/kg, sc). Repeated morphine (5 mg/kg, sc) administration
for 9 days developed tolerance and dependence, bupropion (5 mg/kg, ip) was concurrently
administered to evaluate its potential to modulate these processes. We also biochemically
analyzed bupropion effect on these phenomena through modulation of neurotransmitters
(glutamate and norepinephrine), inflammatory status (nitric oxide), and pro-antioxidant balance
(malondialdehyde and reduced glutathione).
Results
Bupropion was devoid of intrinsic analgesic activity and did not enhance morphine acute
analgesia. However, bupropion significantly attenuated morphine tolerance and dependence
development and abstinence syndrome with corresponding suppression of morphine induced
changes in glutamate, norepinephrine, inflammatory status, and prooxidant-antioxidant balance.
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Conclusion
Bupropion efficacy in attenuation of morphine tolerance and dependence with its high
safety and tolerability profile provide an alternative option to conventional agents e.g., ketamine
and clonidine to modulate these phenomena.