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Development of super sensitivity of apo morphine induced increases in acetyl choline levels and stereotypy after chronic fluphenazine treatment

Development of super sensitivity of apo morphine induced increases in acetyl choline levels and stereotypy after chronic fluphenazine treatment

Neuropharmacology 17(1): 59-64

Dopamine agonists administered systemically produce an increase in striatal levels of acetylcholine (ACh). Possible development of postsynaptic dopamine receptor supersensitivity after neuroleptic treatment was studied by measurement of apomorphine (APO)-induced increase in ACh levels in the striatum and olfactory tubercle. APO-induced stereotypic behavior was also measured. Rats received a single s.c. injection of either sesame seed oil vehicle or fluphenazine (FLU) decanoate (10 mg/kg -1), a long-acting neuroleptic preparation. After 14 days, rats received APO i.p., in various doses (0.03-1.0 mg/kg). After 15 min, brain tissue was rapidly fixed by microwave irradiation, dissected, and ACh levels determined by means of gas chromatography. ACh levels were 75 nmol/g in olfactory tubercle and 70 nmol/g in striatum. APO treamtent resulted in dose-dependent increases of ACh level in both regions. APO-induced increases were greater in rats pretreated with FLU than in controls. Using 0.1 mg/kg APO, the higher striated ACh-elevating effect found 14 days after FLU treatment was also present 21 days, but not 27 days after FLU treatment. At 21 days after s.c. injection, 0.25 mg/kg APO induced significantly greater stereotypic behavior in FLU-treated rats than in controls. FLU treatment led to an apparent temporary supersensitivity of APO-induced increases in ACh levels and stereotypic behavior.

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Accession: 005135561

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PMID: 565881

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