Clonidine has been used successfully in the treatment of
opiate dependence. The discomforting effects of withdrawal are attenuated by the
drug. The question of whether the more central process of dependence is affected by
clonidine was tested in the present study. Change in plasma
corticosterone was used as the indication of the stress of acute withdrawal from
morphine. Conscious, unrestrained male rats showed a dose-related, though somewhat delayed, increase in plasma
corticosterone after
clonidine (0.01-0.1 mg/kg). The suggested mechanism for this effect involves presynaptic inhibition of noradrenergic neurons inhibiting CRF (
corticotropin-releasing factor) release. Similar animals showed an elevation of plasma
corticosterone after
naloxone (0.4 mg/kg) was administered 3 hrs following a single
morphine-priming (10 mg/kg). The
naloxone-precipitated response was unaffected by
clonidine (0.04 mg/kg). This dose of
clonidine did not substitute for
morphine-priming to produce the
naloxone-precipitated response. The data suggests that
clonidine elevated plasma
corticosterone by an indirect mechanism. Further, the stress associated with acute withdrawal is unaffected by
clonidine suggesting that the
drug does not alter dependence development.