Assessment of endogenous opioid mediation in stress-induced hypercholesterolemia in the rat

Stressful stimuli are known to elevate total plasma cholesterol levels and activate endogenous opioid systems. In cholesterol-cholic, acid-fed female rats, a 5-day unpredictable immobilization stress paradigm increased levels of low plus very low density lipoprotein cholesterol and reduced levels of high density lipoprotein cholesterol. Pretreatment with the opiate antagonist, naltrexone (1.0 mg/kg, sc) prevented the stress-induced changes. Five-day morphine pellet implants (75 mg) duplicated the cholesterol alterations seen in immobilized rats. In addition, plasma triglyceride levels were elevated in morphine pelleted rats, but hepatic and aortic cholesterol levels were unchanged. Unchanged plasma sorbitol dehydrogenase activity and hepatic triglyceride levels indicated that both regimens were not hepatotoxic. These findings support the possible role for endogenous opioid systems in stress-induced hypercholesterolemia.