The effect of streptozotocin-induced diabetes on dopamine₂, serotonin(1A) and serotonin(2A) receptors in the rat brain

The effect of streptozotocin (STZ)-induced diabetes and a combination of chronic treatment with haloperidol (HPD) on dopamine (DA)D₂, serotonin (5-HT) 5-HT(1A) and 5- HT(2A) 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-HT(1A)), acid [³H]ketanserin in the frontal cortex (5-HT(2A)). 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-HT(2A) 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-HT(1A) receptors. The affinity constants for D₂, 5-HT(1A), and 5-HT(2A) 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-HT(2A) 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.