Surgical anaesthesia with pentobarbital prevents the effect of local SCH 23390 on rat striatal acetylcholine release in a strain-dependent manner.
This study was performed in order to clarify existing discrepancies about the ability of the D1 antagonist SCH 23390 to reduce striatal acetyicholine (ACh) release after intrastriatal application by reverse dialysis. The possibility that negative findings were related to the use of pentobarbital rather than Equithesin as surgical anaesthesia for implanting microdialysis probes, and of Wistar rather than Sprague-Dawley rats, was tested. SCH 23390, applied by reverse dialysis at the concentration of 24µM, although able to reduce dialysate ACh in male Wistar rats implanted under Equithesin anaesthesia, failed to do so in rats of the same strain implanted 24h or 3 days earlier under pentobarbital anaesthesia. In male Sprague-Dawley rats, local SCH 23390 (24µM) reduced striatal dialysate ACh, both in rats implanted under Equithesin as well as in rats implanted under pentobarbital anaesthesia. Systemic SCH 23390 (0.3mg/kg s.c.) reduced dialysate A Ch both in Wistar and in Sprague-Dawley rats implanted under pentobarbital anaesthesia, but was more effective in the Sprague-Dawley strain. These observations, although consistent with a striatal localization of D1-receptors controlling ACh release, can be explained as being the result of a strain-dependent barbiturate-induced inactivation of D1-mediated control of ACh transmission, which is potentiated by the local changes induced by microdialysis probe implant.
Istituto di Ricerche Farmacologiche Mario Negri, Milan University of Cagliari, Cagliari, Italy.
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Consolo
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Colli
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Caltavuturo
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Di Chiara