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Evidence of an immune system to brain communication axis that affects central opioid functions: muramyl peptides
P M Dougherty1, D B Drath, N Dafny
1Department of Neurobiology and Anatomy, University of Texas Medical School, Houston 77025.
Abstract:
Muramyl peptides are metabolic breakdown products of bacterial cell walls formed in vivo by the reticuloendothelial system. These agents have a variety of immune modulatory and neuropharmacologic effects. It has previously been demonstrated that a variety of immune modifying agents can induce alterations in certain behaviors elicited by opiates. In the present study we investigate possible reciprocal interactions between muramyl dipeptides (MDPs) and central opioid systems using three different experimental models: (1) naloxone-precipitated withdrawal behavior in morphine-dependent rats; (2) the tail immersion assay for determination of morphine-induced antinociception and (3) rectal temperature measurement of the pyrogenic activity of MDP. It is shown that two derivatives of MDP attenuate the severity of naloxone-precipitated withdrawal and morphine-induced antinociception. In addition, it is demonstrated that the pyrogenic activity of a stearoyl derivative of MDP is altered by chronic morphine treatment. These findings suggest both novel neuropharmacologic properties of muramyl dipeptides, as well as demonstrate that yet another immune modifier interacts with centrally mediated opioid phenomena.
Insights
Muramyl peptides (MDPs) can reduce opioid withdrawal symptoms and pain sensitivity in rats. Chronic morphine treatment also affects the fever-inducing properties of MDPs, suggesting complex immune and opioid system interactions.
Area of Science:
- Neuropharmacology
- Immunology
- Microbiology
Background:
- Muramyl peptides (MDPs) are bacterial cell wall breakdown products with immune-modulatory and neuropharmacologic effects.
- Immune modifiers can alter behaviors related to opioid use.
- Reciprocal interactions between MDPs and central opioid systems are not well understood.
Purpose of the Study:
- To investigate the interactions between muramyl dipeptides (MDPs) and central opioid systems.
- To determine if MDPs affect opioid withdrawal, analgesia, and pyrogenic responses.
Main Methods:
- Three experimental models were used: naloxone-precipitated withdrawal in morphine-dependent rats, tail immersion assay for morphine-induced antinociception, and rectal temperature measurement for MDP pyrogenic activity.
- Two MDP derivatives were tested for their effects on withdrawal and antinociception.
- The pyrogenic activity of a stearoyl MDP derivative was assessed in chronically morphine-treated rats.
Main Results:
- MDP derivatives significantly attenuated naloxone-precipitated withdrawal behavior.
- MDP derivatives reduced morphine-induced antinociception.
- Chronic morphine treatment altered the pyrogenic activity of a stearoyl MDP derivative.
Conclusions:
- Muramyl dipeptides exhibit novel neuropharmacologic properties.
- MDPs interact with central opioid systems, influencing withdrawal and pain perception.
- These findings highlight a new immune modifier that interacts with opioid phenomena.