Pharmacological studies on stress-induced increase in frontal cortical dopamine metabolism in the rat.
The effects of a variety of minor tranquilizers and of benzodiazepine inverse agonists on the stress-induced increase in frontal cortical dopamine metabolism have been studied in the rat. Electric footshock stress increased 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the frontal (but not parietal) cortex and in the nucleus accumbens but not in the striatum or ventral tegmental area. Similar stress-induced alterations of frontal cortical DOPAC levels were observed after DSP4-induced noradrenergic denervation or after adrenalectomy. Other types of stress, e.g. conditioned fear (exposure to an environment paired previously with footshock) or swim stress also provoked an elevation of DOPAC levels in the prefrontal cortex. When administered systemically, the anxiolytic agents meprobamate, CL 218,872, CGS 9896, suriclone and the hypnotic/anxiolytic drugs zolpidem and zopiclone all prevented the electric footshock stress-induced augmentation of cortical DOPAC levels whereas the gamma-aminobutyric acid receptor agonists progabide, muscimol and depamide or the sedative alpha-1 adrenoceptor antagonist prazosin were ineffective. The preventive effect of diazepam and zolpidem on the stress-induced biochemical response was antagonized by the benzodiazepine antagonist CGS 8216 but not by the gamma-aminobutyric acid receptor antagonist bicuculline. In nonstressed rats, systemic administration of the anxiogenic benzodiazepine inverse agonists beta-CCM (methyl-beta-carboline-3-carboxylate) and beta-CCE (ethyl-beta-carboline-3-carboxylate), but not of the benzodiazepine antagonists Ro 15-1788 or CGS 8216, caused an increase in frontal cortical DOPAC similar to that provoked by stress and which was antagonized by zolpidem.(ABSTRACT TRUNCATED AT 250 WORDS)
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004597:Electroshock; D005239:Fear / Q000502:physiology; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects; D013312:Stress, Physiological / Q000378:metabolism*; D013550:Swimming; D000077334:Zolpidem
D014151:Anti-Anxiety Agents; D002243:Carbolines; D011725:Pyridines; D011954:Receptors, Dopamine; D011963:Receptors, GABA-A; D015102:3,4-Dihydroxyphenylacetic Acid; C024915:beta-carboline-3-carboxylic acid ethyl ester; D000077334:Zolpidem; C036150:beta-carboline-3-carboxylic acid methyl ester; D004298:Dopamine