Effects of amisulpride, an atypical antipsychotic which blocks preferentially presynaptic dopamine autoreceptors, on integrated functional cerebral activity in the rat.
Amisulpride, a benzamide derivative with an atypical neuroleptic profile relieves the negative symptoms of schizophrenia when administered at low doses (50-150 mg). In an attempt to define the anatomical substrates involved in this action we have studied the effects of amisulpride on regional cerebral glucose utilisation (RCGU) in the awake lightly restrained rat, by quantitative autoradiography using [14C]2-deoxyglucose ([14C]2-DG). Amisulpride was administered 1 h before [14C]2DG i.v. injection, at a dose of 5 mg/kg which resulted in a striatal D2 receptor occupancy of 10% similar to that induced by doses of this compound used for the treatment of negative symptoms of schizophrenia. Amisulpride induced significant RCGU increases in cortical areas, in visual relays, in auditory structures and in several limbic structures. The pattern of changes in RCGU seen with amisulpride clearly differs from that of haloperidol, given at a dose resulting in a similar occupancy of striatal D2 receptors (0.01 mg/kg), which was mostly ineffective. The amisulpride-induced activation of RCGU in specific brain areas involved in the control of cognitive functions and motivational and emotional behavior, may at least in part, explain the efficacy of this compound in the treatment of negative symptoms of schizophrenia.
Cudennec
A
A
Synthélabo Recherche, Recherche SNC, Bagneux, France.
Fage
D
D
Bénavidès
J
J
Scatton
B
B
D000077582:Amisulpride; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001306:Auditory Pathways / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D005116:Extrapyramidal Tracts / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D008297:Male; D009415:Nerve Net / Q000187:drug effects*; D017729:Presynaptic Terminals / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013469:Sulpiride / Q000031:analogs & derivatives* / Q000494:pharmacology; D014055:Tomography, Emission-Computed; D014795:Visual Pathways / Q000187:drug effects
D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D013469:Sulpiride; D000077582:Amisulpride; D003847:Deoxyglucose; D005947:Glucose