Development of supersensitivity of apomorphine-induced increases in acetylcholine levels and stereotypy after chronic fluphenazine treatment

Abstract

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. Apomorphine-induced Stereotypic behaviour was also measured. Rats received a single subcutaneous injection of either sesame seed oil vehicle or fluphenazine (FLU) decanoate (10mg kg −1), a long-acting neuroleptic preparation. After 14 days, rats received APO intraperitoneally, in various doses (0.03–1.0 mg kg −1). Fifteen minutes later, brain tissue was rapidly fixed by microwave irradiation, dissected, and ACh levels determined by means of gas chromatography. Acetylcholine levels were 75nmol g −1 in olfactory tubercle and 70 nmol g −1 in striatum. Apomorphine treatment resulted in dose-dependent increases of ACh level in both regions. Apomorphine-induced increases were greater in rats pretreated with FLU than in controls. Using 0.1 mg kg −1 APO, the higher striatal 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 subcutaneous injection, 0.25 mg kg −1 APO induced significantly greater Stereotypic behaviour in FLU-treated rats than in controls. Thus. FLU treatment led to an apparent temporary supersensitivity of APO-induced increases in ACh levels and stereotypic behaviour.