Preferential decrease in dopamine utilization in prefrontal cortex by zopiclone, diazepam and zolpidem in unstressed rats.
This study has compared the effects of a cyclopyrrolone, zopiclone, a benzodiazepine, diazepam, and an imidazopyridine, zolpidem, on dopamine (DA) and DOPAC levels, and DA utilization (DOPAC/DA ratio) in rat striatum and prefrontal cortex. The endogenous levels of DA were significantly increased by both zopiclone (2.5, 10 and 40 mg kg-1 p.o.) and diazepam (10 and 40 mg kg-1 p.o.) in the prefrontal cortex, whereas striatal DA content was significantly increased only with the highest dose of diazepam (40 mg kg-1 p.o.). Diazepam (10 and 40 mg kg-1 p.o.) decreased cortical level of DOPAC more markedly than striatal levels, whereas zopiclone (40 mg kg-1 p.o.) only slightly decreased striatal DOPAC levels. Zopiclone and diazepam dose-dependently decreased DA utilization, an effect which was more marked in prefrontal cortex than in striatum. This result was confirmed with zolpidem, another benzodiazepine ligand. Zopiclone was most potent at decreasing DA utilization at the cortical level. The diazepam-induced decreases in DA metabolism and utilization were antagonized by Ro 15-1788, suggesting that the effects seen were mediated by specific benzodiazepine receptors. Thus, our results clearly show that ligands acting on the benzodiazepine receptor GABA receptor chloride ionophore complex can decrease the utilization of dopamine in unstressed rats. The preferential decrease in cortical DA utilization induced by benzodiazepine ligands may be compared to the well-known activation by stress of the mesocortical DAergic system.
Boireau
A
A
Rhône-Poulenc Santé, Centre de recherche de Vitry-Alfortville, Vitry-sur-Seine, France.
Dubedat
P
P
Laduron
P M
PM
Doble
A
A
Blanchard
J C
JC
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism*; D000818:Animals; D053961:Azabicyclo Compounds; D002540:Cerebral Cortex / Q000737:chemistry / Q000378:metabolism*; D003342:Corpus Striatum / Q000737:chemistry / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism* / Q000627:therapeutic use; D005442:Flumazenil / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013312:Stress, Physiological / Q000378:metabolism; D000077334:Zolpidem
D053961:Azabicyclo Compounds; D010879:Piperazines; D011725:Pyridines; C515050:zopiclone; D015102:3,4-Dihydroxyphenylacetic Acid; D005442:Flumazenil; D000077334:Zolpidem; D003975:Diazepam; D004298:Dopamine