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Peripheral effects of methionine-enkephalin on inflammatory reactions and behavior in the rat
V Vujić-Redzić1, M Dimitrijević, S Stanojević
1Immunology Research Center 'Branislav Jankovic', School of Medicine, Belgrade, Yugoslavia.
Abstract:
Methionine-enkephalin (Met-Enk) induces notable alterations in immune and central nervous system functions. The present study was conducted in order to compare peripheral and central effects of Met-Enk on nonspecific immunity, open field behavior and pain perception in the rat. The results showed that 0.2 mg/kg of Met-Enk given intraperitoneally (i.p.) increased concanavalin A (Con-A)-induced paw edema and enhanced basal and phorbol myristate acetate (PMA)-stimulated H(2)O(2) production of peritoneal macrophages. Met-Enk-induced immunopotentiation was antagonized by anti-Met-Enk antibodies (anti-Met-Enk-Ig) and quaternary naltrexone (qNtx). Met-Enk injected i.p. produced an increase of horizontal and vertical locomotor activity in the open field that was reversed by i. p. administration of anti-Met-Enk-Ig and qNtx. The dose of 0.2 mg/kg of Met-Enk applied i.p. did not affect the number of writhes in the test of analgesia. Intracerebroventricular (i.c.v.) injection of Met-Enk, given in a dose that was previously shown to be immunostimulatory, enhanced only basal H(2)O(2) production of peritoneal macrophages, and anti-Met-Enk-Ig antagonized this effect. Besides, i.c.v. treatment with anti-Met-Enk-Ig increased and decreased H(2)O(2) production of peritoneal macrophages under basal and stimulated conditions, respectively. Met-Enk and anti-Met-Enk-Ig injected i.c.v. did not influence activity in the open field and pain sensitivity. Thus, the i.c.v. dose of Met-Enk that was sufficient to modulate immune functions did not influence behavior. It may be concluded that Met-Enk modulated nonspecific immune responses and open field behavior by peripheral mechanisms.
Insights
Methionine-enkephalin (Met-Enk) primarily affects immune responses and behavior through peripheral pathways, not central ones. This study found Met-Enk
Area of Science:
- Neuroimmunology
- Behavioral Neuroscience
- Pharmacology
Background:
- Methionine-enkephalin (Met-Enk) is an endogenous opioid peptide known to influence both the immune system and central nervous system (CNS).
- Understanding the distinct roles of peripheral versus central Met-Enk administration is crucial for elucidating its mechanisms of action.
Purpose of the Study:
- To compare the peripheral and central effects of Met-Enk on nonspecific immunity, open field behavior, and pain perception in rats.
- To investigate the specific routes through which Met-Enk exerts its immunomodulatory and behavioral effects.
Main Methods:
- Rats received Met-Enk via intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration.
- Nonspecific immunity was assessed by measuring Concanavalin A (Con-A)-induced paw edema and peritoneal macrophage hydrogen peroxide (H2O2) production.
- Open field tests were used to evaluate locomotor activity, and analgesia was assessed using a writhe test.
- Effects were further analyzed using anti-Met-Enk antibodies (anti-Met-Enk-Ig) and quaternary naltrexone (qNtx).
Main Results:
- Peripheral (i.p.) Met-Enk administration potentiated immune responses, including increased paw edema and enhanced macrophage H2O2 production, effects blocked by anti-Met-Enk-Ig and qNtx.
- Intraperitoneal Met-Enk increased locomotor activity in the open field, an effect also reversed by anti-Met-Enk-Ig and qNtx.
- Intracerebroventricular (i.c.v.) Met-Enk administration enhanced only basal H2O2 production, with no significant effects on open field behavior or pain perception.
- Central administration of anti-Met-Enk-Ig modulated macrophage H2O2 production differently under basal and stimulated conditions.
Conclusions:
- Methionine-enkephalin modulates nonspecific immune responses and open field behavior predominantly through peripheral mechanisms.
- Central administration of Met-Enk, even at immunostimulatory doses, did not significantly alter behavior or pain sensitivity.
- The findings suggest that the immunomodulatory and behavioral effects of Met-Enk are largely mediated via peripheral pathways, distinct from direct central actions.