Benzodiazepine prevention of swim stress-induced sensitization of cortical biogenic amines: an in vivo microdialysis study.
In vivo microdialysis was used to determine the effect of diazepam, flumazenil and FG-7142 upon the biogenic amine response to acute and repeated swim stress in the medial prefrontal cortex of the rat. Acute swim stress increased norepinephrine levels, although dopamine and serotonin levels remained stable. Upon re-exposure to swim stress twenty-four hours later, sustained increases (200-300% of baseline) in all three biogenic amines were detected. This enhanced response to re-stress was not seen in rats pretreated with either a benzodiazepine: agonist (diazepam, 2 mg/kg), an antagonist (flumazenil, 10 mg/kg), or an inverse agonist (FG-7142, 10 mg/kg) given prior to the first swim stress. Therefore, the sensitization of biogenic amine response to re-stress may be prevented by compounds which differ in their activity at the benzodiazepine receptor.
Petty
F
F
Veterans Affairs Medical Center, University of Texas Southwestern Medical School, Dallas 75216, USA. PETTY.FREDERICK/DALLAS.VA.GOV
Jordan
S
S
Kramer
G L
GL
Zukas
P K
PK
Wu
J
J
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001679:Biogenic Amines / Q000096:biosynthesis*; D002243:Carbolines / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D005442:Flumazenil / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000188:drug therapy* / Q000378:metabolism; D013550:Swimming / Q000502:physiology
D014151:Anti-Anxiety Agents; D001679:Biogenic Amines; D002243:Carbolines; D018755:GABA Agonists; D018756:GABA Antagonists; D005442:Flumazenil; C035874:FG 7142; D003975:Diazepam