title: Clonidine prevents methylxanthine stimulation of norepinephrine metabolism in rat brain.
abstract: Methylxanthines can produce behavior resembling opiate withdrawal in rats. Since previous studies have demonstrated the involvement of central noradrenergic systems during naloxone-precipitated withdrawal, the effects of 3-isobutyl-1-methylxanthine (IBMX) on norepinephrine metabolism in rat brain were studied. It was found that administration of IBMX elevated levels of the major norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in areas innervated by the locus coeruleus. The increases in MHPG was noted 1 h after administration and was maximal (270% of control) after 3 h. Levels of another norepinephrine metabolite, 3,4-dihydroxyphenylglycol, followed a similar pattern and time course. Coadministration of naloxone with IBMX did not affect the IBMX-induced elevation in MHPG. Administration of the alpha-agonist clonidine, however, antagonized the effects of IBMX on MHPG levels. The effects of IBMX and clonidine were dose dependent; the lowest dose of IBMX needed to elevate MHPG was 30 mumol/kg (i.p.), and clonidine (180 nmol/kg) reduced the effect of IBMX (100 mumol/kg) by 50%. The data, discussed in terms of a methylxanthine-noradrenergic interaction, suggest that withdrawal behaviors in general may be subserved by hyperactive noradrenergic neurons.
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013806:Theophylline / Q000031:analogs & derivatives*
chemical_list: D009270:Naloxone; D013806:Theophylline; D003000:Clonidine; D003975:Diazepam; D015056:1-Methyl-3-isobutylxanthine; D009638:Norepinephrine