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Increased S(−)-Apomorphine–Induced Vacuous Chewing and Attenuated Effect of Chronic Haloperidol Treatment in Streptozotocin-Induced Diabetic Rat

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Abstract

The incidence of S(−)-apomorphine–induced vacuous chewing movements (VCMs) as a model for tardive dyskinesia was investigated in streptozotocin (STZ)-induced diabetic rats. A single dose of STZ (65 mg/kg, intravenously) caused a diabetic state (hyperglycemia, 480–490 vs. 116–118 mg/dl in naive rats). S(−)-apomorphine (250 μg/kg, subcutaneously)–induced VCMs were significantly intensified in diabetic rats which had received STZ 9 weeks previously. The enhancement of VCMs was also observed in nondiabetic rats which received subsequent treatment with depot haloperidol (4 mg/kg, intramuscularly, once a week, every week for 4 weeks) followed by a 2-week washout period. The ability of haloperidol to enhance VCMs was attenuated in diabetic rats. The implications of these results in relation to altered neurotransmissions in STZ-induced diabetes are discussed.

Section snippets

Method

Male Sprague–Dawley rats (Zivic Miller Laboratories, Pittsburgh, PA), weighing 200–250 g on arrival in the laboratory, were used. The rats were housed in groups of five or six in standard floor net cages in a light- and temperature-controlled room and had free access to food and water.

Animals were rendered diabetic according to an established protocol [2]. STZ (65 mg/kg, in 0.01 M citrate buffer, pH 4.5, 1 ml/kg; Sigma Chemical Co., St. Louis, MO) was injected into the lateral tail vein. An

Results

STZ-treated rats showed a loss of weight gain which continued throughout the study period (Table 1). Blood glucose levels in STZ-induced DM rats 1 week after STZ treatment (STZ–HPD and STZ–vehicle groups) were elevated about fourfold compared with non-DM rats (vehicle–HPD and vehicle–vehicle groups) (Table 2). All rats assigned to the DM groups (STZ–HPD and STZ–vehicle) were found to be hyperglycemic (blood glucose > 332 mg/dl). Diabetes was also verified by glucosuria (Chemstrip; Boehringer

Discussion

The present study provides the first evidence for enhancement of S(−)-apomorphine–induced VCMs in STZ-induced DM rats. Moreover, the results confirm the previous finding of an increased incidence of apomorphine-induced VCMs following chronic neuroleptic treatment [31]. The present findings also demonstrated a lower incidence of S(−)-apomorphine–induced VCMs in rats receiving both HPD and STZ relative to animals receiving HPD alone.

The present study used 250 μg/kg S(−)-apomorphine, a dose which

Acknowledgements

The authors are grateful to H. A. Johnston for research assistance and L. Mason for secretarial assistance. This research was supported in part by the National Alliance for Research on Schizophrenia and Depression.

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