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The objective of this manuscript is to summarize studies that demonstrate that the immune system participates in the expression of opiate withdrawal. Five groups of animals were used: 1. Chronic morphine control group; 2. The immune system was ablated in morphine-dependent rats; 3. In morphine-dependent animals the immune system was ablated and followed by reconstitution of the immune system from intact normal donor animals; 4.The immune system was ablated prior to chronic morphine exposure; and, 5. The immune system in morphine-naïve animals was ablated followed by immune component reconstitution from donor animals and then exposed to chronic morphine. All of the chronic morphine exposure animals were injected with 1.0 mg/kg naloxone to precipitate the behavioral withdrawal symptoms. In the first group, naloxone precipitated the classical behavioral syndrome; in groups 2 and 4 withdrawal symptoms were significantly attenuated and eliminated in some animals; and, in groups 3 and 5 naloxone injection resulted in severe withdrawal behavior. These experiments demonstrated that the immune system participates in opiate withdrawal expression and suggest the use of immunotherapy to control the opioid epidemic.

Evidence that the Immune System Participates in the Expression of Opiate Withdrawal Behavior