title: Increased striatal acetylcholine after 14 months cis-flupenthixol treatment in rats suggests functional supersensitivity of dopamine receptors.
abstract: Rats received continuous administration of cis-flupenthixol (0.8-1.2 mg/kg/day) or trans-flupenthixol (0.9-1.2 mg/kg/day) in drinking water for 14 months. The administration of cis-flupenthixol, but not trans-flupenthixol, caused apparent cerebral dopamine receptor supersensitivity. Thus, animals receiving cis-flupenthixol, but not trans-flupenthixol, showed enhanced apo-morphine-induced stereotyped behaviour. Dopamine concentration in striatum was not altered by drug treatment but striatal HVA and DOPAC concentrations were reduced in animals receiving cis-flupenthixol, but not trans-flupenthixol. No consistent change in Bmax of KD for specific striatal 3H-spiperone binding was observed after 14 months drug intake. However, in cis-flupenthixol treated animals a 40% increase in Bmax was observed following 2 weeks drug withdrawal. Continuous cis-flupenthixol intake increased striatal acetylcholine concentrations; trans-flupenthixol was without effect. This suggests the apparent increase in cerebral dopamine receptor supersensitivity caused by continuous long-term cis-flupenthixol administration is of functional importance in the intact animal.
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D005475:Flupenthixol / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013237:Stereoisomerism; D013239:Stereotyped Behavior / Q000187:drug effects; D013892:Thioxanthenes / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D011954:Receptors, Dopamine; D013892:Thioxanthenes; D005475:Flupenthixol; D001058:Apomorphine; D000109:Acetylcholine