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.

• Authors: Jun-Li Cao, Hai-Lei Ding, Li-Cai Zhang, Shi-Ming Duan, Yin-Ming Zeng
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 23 Issue 8 Pg. 685-90 (Aug 2002) ISSN: 1671-4083 [Print] United States
• PMID: 12147189 (Publication Type: Journal Article)

Chemical References

• Anti-Anxiety Agents
• Oncogene Proteins v-fos
• Naloxone
• Adenosine Monophosphate
• Midazolam

Topics

• Adenosine Monophosphate (metabolism)
• Animals
• Anti-Anxiety Agents (pharmacology)
• Mice
• Midazolam (pharmacology)
• Morphine Dependence
• Naloxone (pharmacology)
• Oncogene Proteins v-fos (metabolism)
• Rats
• Rats, Sprague-Dawley
• Spinal Cord (metabolism)
• Substance Withdrawal Syndrome (metabolism, prevention & control)