Differential effects of abecarnil on basal release of acetylcholine and dopamine in the rat brain.
Abecarnil (0.1-1 mg/kg i.p.), a new anxioselective and anticonvulsant ligand of benzodiazepine receptors, like diazepam (2.5-10 mg/kg i.p.) inhibited in a dose-dependent manner the basal release of acetylcholine in the hippocampus of freely moving rats. In contrast, whereas diazepam inhibited the basal output of dopamine in the prefrontal cortex, abecarnil had no such effect. The effects of both abecarnil and diazepam were antagonized by prior treatment with flumazenil at a dose (1 mg/kg i.p.) that per se had no effect on acetylcholine or dopamine release. The results suggest that abecarnil has different intrinsic efficacies at gamma-aminobutyric acid type A (GABAA) receptors involved in the regulation of acetylcholine release in the hippocampus and dopamine release in the prefrontal cortex, two brain areas important in cognitive function and emotional state, respectively.
Imperato
A
A
Department of Neuroscience B.B. Brodie, University of Cagliari, Italy.
Dazzi
L
L
Serra
M
M
Gessa
G L
GL
Biggio
G
G
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002243:Carbolines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003975:Diazepam / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D005442:Flumazenil / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D014151:Anti-Anxiety Agents; D002243:Carbolines; D058785:GABA-A Receptor Agonists; D005442:Flumazenil; C062769:abecarnil; D000109:Acetylcholine; D003975:Diazepam; D004298:Dopamine