Opposite effects of midazolam and beta-carboline-3-carboxylate ethyl ester on the release of dopamine from rat nucleus accumbens measured by in vivo microdialysis.
This report describes the effects of midazolam and beta-carboline-3-carboxylate ethyl ester (beta-CCE) on extracellular concentrations of dopamine in the nucleus accumbens of freely moving rats measured by in vivo microdialysis. The two compounds had opposite effects, midazolam (0.075 and 0.15 mg/kg i.v.) dose dependently decreasing, and beta-CCE (3 and 10 mg/kg i.p.) dose dependently increasing, dialysate concentrations of dopamine. Flumazenil (6 micrograms/kg i.v.) did not affect the efflux of dopamine but it prevented the effects of both midazolam and beta-CCE on dopamine efflux. N6-Cyclohexyladenosine (0.1, and 1 mg/kg i.p.), a selective adenosine A1 agonist, dose dependently increased the efflux of dopamine. This effect was blocked by 8-cyclopentyl-1,3-dipropylxanthine (25 mg/kg i.p.), a selective adenosine A1 receptor antagonist, a dose which given alone did not affect dopamine efflux; responses to midazolam were not affected. 3,7-Dimethyl-1-propargylxanthine (1 and 3 mg/kg i.p.), a selective adenosine A2 receptor antagonist, did not mimic the effects of beta-CCE. The results suggest that midazolam and beta-CCE modulate dopamine release in the nucleus accumbens by an action at the benzodiazepine binding site associated with the GABAA receptor complex.
Murai
T
T
Department of Dental Anesthesiology, Nihon University School of Dentistry, Tokyo, Japan.
Koshikawa
N
N
Kanayama
T
T
Takada
K
K
Tomiyama
K
K
Kobayashi
M
M
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002243:Carbolines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology; D008024:Ligands; D008297:Male; D017551:Microdialysis; D008874:Midazolam / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology; D013805:Theobromine / Q000031:analogs & derivatives / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D002243:Carbolines; D008024:Ligands; D058915:Purinergic P1 Receptor Antagonists; D011963:Receptors, GABA-A; D014970:Xanthines; C027513:N(6)-cyclohexyladenosine; D005442:Flumazenil; D013779:Tetrodotoxin; C057837:3,7-dimethyl-1-propargylxanthine; C024915:beta-carboline-3-carboxylic acid ethyl ester; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine; D013805:Theobromine; D008874:Midazolam; D004298:Dopamine