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Neuropsychopharmacology (1997) 16 183-190.
The Effect of Streptozotocin-Induced Diabetes on Dopamine2, Serotonin1A and Serotonin2A Receptors in the Rat Brain
Tomiki Sumiyoshi MD, Ph.D, Junji Ichikawa MD, Ph.D and Herbert Y Meltzer MD |
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From the Department of Psychiatry, Case Western Reserve University School of Medicine, Cleveland, OH
Correspondence: Tomiki Sumiyoshi, MD, Ph.D, Department of Neuropsychiatry, Toyama Medical and Pharmaceutical University, Faculty of Medicine, 2630 Sugitani, Toyama 930-01, Japan
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ABSTRACT
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The effect of streptozotocin (STZ)-induced diabetes and a combination of chronic treatment with haloperidol (HPD) on dopamine (DA)D2, serotonin (5-HT) 5-HT1A and 5-HT2A receptors was investigated in rat brain. Rats were randomly assigned to one of four groups: vehicle-vehicle, STZ-vehicle, vehicle-HPD, and STZ-HPD groups. Four weeks after single administration of STZ (65 mg/kg IV) or vehicle (citrate buffer), rats received depot HPD (4 mg/kg IM) or vehicle (sesame oil) once a week for 4 weeks. Sixteen days after the last injection of HPD or vehicle, rats were sacrificed, and the density of binding sites was determined using [3H]spiperone as ligand in the striatum (D2), [3H]8-hydroxy-2-(di-n-propyl)-aminotetraline in the hippocampus (5-HT1A), and [3H]ketanserin in the frontal cortex (5-HT2A). The density of D2 receptors was significantly increased in the vehicle-HPD compared to vehicle-vehicle controls. However, striatal D2 receptor density of the STZ-HPD and the STZ-vehicle were not significantly different from the vehicle-vehicle group. A significant increase in cortical 5- HT2A receptor density was observed only in the group of STZ-vehicle. Treatment with STZ, HPD, or the combination thereof, did not affect the density of 5-HT1A receptors. The affinity constants for D2, 5-HT1A, and 5-HT2A receptors were not affected by any treatment. These results suggest that diabetic state may affect brain serotonergic activity via an increase in the density of 5-HT2A receptors. This may indicate an increased vulnerability to major depression in patients with diabetes. The lack of an effect of the combined chronic treatment with STZ and HPD on the D2 receptor density may correspond to the increased risk to develop tardive dyskinesia in patients with diabetes.
Keywords: Diabetes; Streptozotocin; Dopamine-D2 receptors; Serotonin1A receptors; Serotonin2A receptors; Haloperidol; Major depression; Tardive dyskinesia |
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