Anxiogenic beta-carboline FG 7142 produces activation of noradrenergic neurons in specific brain regions of rats.
By measuring the levels of two major metabolites of rat brain noradrenaline (NA), 3-methoxy-4-hydroxyphenylglycol (MHPG) and 3,4-dihydroxyphenylglycol (DHPG), we investigated the effects of anxiogenic beta-carboline FG 7142, an inverse agonist of benzodiazepine (BZD) receptors, on brain noradrenergic activity of rats. Thirty min after treatment with FG 7142 (15 mg/kg IP), levels of both MHPG and DHPG in the hypothalamus, amygdala and thalamus, but not in the hippocampus and cerebral cortex, significantly increased. These increases were significantly antagonized by pretreatment with BZD receptor antagonist Ro 15-1788 (15 mg/kg, IP). Sixty min after treatment with FG 7142 at the same dose, significant increases in both metabolite levels occurred in the hypothalamus, amygdala, thalamus and cerebral cortex, and increases in MHPG levels only were observed in the hippocampus. These increases were significantly blocked by pretreatment with alpha 2-adrenoreceptor agonist clonidine (100 microgram/kg, IP). The present findings suggest that FG 7142 can produce increases in brain noradrenergic activity in specific brain regions by interacting with BZD receptors, and may support the hypothesis that hyperactivity of brain noradrenergic systems may be one neural mechanism in provocation of aversive emotional changes (anxiety, fear or panic).
Ida
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Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510.
Elsworth
J D
JD
Roth
R H
RH
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002243:Carbolines / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology; D005442:Flumazenil / Q000494:pharmacology; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D009638:Norepinephrine / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D002243:Carbolines; D005442:Flumazenil; D008734:Methoxyhydroxyphenylglycol; C035874:FG 7142; D003000:Clonidine; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine