Local administration of flurazepam has different effects on dopamine release in striatum and nucleus accumbens: a microdialysis study.
The action of local administration of flurazepam on extracellular levels of dopamine (DA) and its metabolites 3,4 dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA) in the anterior striatum and medial nucleus accumbens have been investigated using microdialysis. Flurazepam (10 microM), administered through the perfusion medium for 20 min, reduced levels of DA in dialysates from the nucleus accumbens by 60% while the same concentration of the drug had no effect on levels of DA in perfusates from the striatum. Pretreatment with the benzodiazepine antagonist Ro 15-1788 (flumazenil) or with picrotoxin, a drug which blocks the GABAA receptor-associated chloride channel, inhibited the effect of flurazepam on levels of DA in the nucleus accumbens, which suggests that the effect was mediated by the multimolecular GABAA/benzodiazepine receptor complex. Administration of flurazepam had little effect on the two metabolites of DA, DOPAC and HVA, in either the nucleus accumbens or striatum. The inverse partial benzodiazepine agonist, FG 7142, had no significant action on the release of DA in the nucleus accumbens. These results suggest that the dopaminergic projection to the nucleus accumbens is more sensitive to benzodiazepine-induced inhibition than the projection to the striatum.
Zetterström
T
T
University Laboratory of Physiology, Oxford, U.K.
Fillenz
M
M
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002243:Carbolines / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism*; D005442:Flumazenil / Q000494:pharmacology; D005479:Flurazepam / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012686:Septal Nuclei / Q000378:metabolism*
D015102:3,4-Dihydroxyphenylacetic Acid; D002243:Carbolines; D004298:Dopamine; D005442:Flumazenil; D005479:Flurazepam; D010852:Picrotoxin; C035874:FG 7142