Influences of Locus Coeruleus Lesions and Reserpine Treatment on Opioid Physical Dependence in Rats

Aim: To study the role of locus coeruleus (LC) noradrenergic neurons in the opioid dependence.

Methods: Chemical lesion of LC was produced by 6-hydroxydopamine (4 micrograms in 1 microL). Reserpine (Res) was used to deplete central noradrenaline. Composite scores of naloxone (4 mg.kg-1, ip) precipitated abstinence syndromes were calculated and the magnitude of weight loss was determined in chronic morphine (Mor)- or dihydroetorphine (DHE)-treated rats.

Results: Lesions of LC made Mor, but not DHE, abstinence syndrome more serious. Multiple doses of Res (0.5 mg.kg-1.d-1 x 3 d) increased scores of Mor and DHE abstinence syndrome, made worse the loss of body weight in chronic Mor-, but not DHE-, treated rats. A single dose of Res (0.5 mg.kg-1) speeded up the development of physical dependence on Mor.

Conclusion: The LC noradrenergic neurons play a role in suppression of some withdrawal symptoms.