title: Influence of clonidine on the acute dependence response elicited in naive rats by naloxone.
abstract: 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.
mesh_terms: D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology*; D009293:Opioid-Related Disorders; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
chemical_list: D009270:Naloxone; D009020:Morphine; D003000:Clonidine; D003345:Corticosterone