Increased striatal acetylcholine after 14 months cis-flupenthixol treatment in rats suggests functional supersensitivity of dopamine receptors |
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Authors: | K Murugaiah S Mann A E Theodorou P Jenner C D Marsden |
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Institution: | 1. University Department of Neurology, Institute of Psychiatry & King''s College Hospital Medical School, Denmark Hill, London SE5, UK;2. Agriculture Research Council, Institute of Animal Physiology, Babraham, Cambridge CB2 4AT, U.K. |
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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. |
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