Pretreatment with midazolam suppresses morphine withdrawal response in mice and rats.
Abstract
AIM: To investigate the roles of pretreatment with midazolam on morphine
withdrawal in mice and rats.
METHODS: Acute and chronic morphine dependence and naloxone-precipitated
withdrawal models were employed in the present study. Cyclic adenosine
monophosphate (AMP) content and Fos protein expression were measured by
radioimmunoassay and immunocytochemistry, respectively.
RESULTS: Coadministration of midazolam (2 mg/kg, ip) and morphine prevented the
development of both acute and chronic morphine dependence in mice. Compared to
saline-morphine group (3.0, 95 % confidence limits: 1.9-4.3 mg/kg), ED50 of
naloxone-precipitated withdrawal jumping increased significantly in
midazolam-morphine group (10.4, 95 % confidence limits: 8.5-12.3 mg/kg) in acute
morphine-dependent mice (P<0.01). Pretreatment with midazolam lowered the number
and incidence of naloxone-precipitated withdrawal jumping and prevented loss in
body weight in chronic morphine-dependent mice (P<0.01). Midazolam-pretreatment
inhibited the increase of Fos protein expression, not cyclic AMP content, in rat
spinal cord during morphine withdrawal.
CONCLUSION: Midazolam suppresses morphine withdrawal response by inhibiting
hypersensitization of the spinal cord neurons, and this effect may not be
mediated by cAMP pathway.
Keywords:
withdrawal in mice and rats.
METHODS: Acute and chronic morphine dependence and naloxone-precipitated
withdrawal models were employed in the present study. Cyclic adenosine
monophosphate (AMP) content and Fos protein expression were measured by
radioimmunoassay and immunocytochemistry, respectively.
RESULTS: Coadministration of midazolam (2 mg/kg, ip) and morphine prevented the
development of both acute and chronic morphine dependence in mice. Compared to
saline-morphine group (3.0, 95 % confidence limits: 1.9-4.3 mg/kg), ED50 of
naloxone-precipitated withdrawal jumping increased significantly in
midazolam-morphine group (10.4, 95 % confidence limits: 8.5-12.3 mg/kg) in acute
morphine-dependent mice (P<0.01). Pretreatment with midazolam lowered the number
and incidence of naloxone-precipitated withdrawal jumping and prevented loss in
body weight in chronic morphine-dependent mice (P<0.01). Midazolam-pretreatment
inhibited the increase of Fos protein expression, not cyclic AMP content, in rat
spinal cord during morphine withdrawal.
CONCLUSION: Midazolam suppresses morphine withdrawal response by inhibiting
hypersensitization of the spinal cord neurons, and this effect may not be
mediated by cAMP pathway.