THE EFFECT OF STREPTOZOTOCIN-INDUCED DIABETES ON DOPAMINE(2), 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)D-2, serot onin (5-HT)5-HT1A and 5-HT2A receptors was investigated in rat brain. Rats were randomly assigned to one of four groups: vehicle-vehicle, ST Z-vehicle, vehicle-HPD, and STZ-HPD groups. Four weeks after single ad ministration of STZ (65 mg/kg IV) or vehicle (seasame 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 [H-3]spiperone as ligand in the striatum (D-2), [H-3]8-hydroxy- 2-(di-n-propyl)-aminotetraline in the hippocampus (5-HT1A), and [H-3]k etanserin in the frontal cortex (5-HT2A). The density of D-2 receptors was significantly increased in the vehicle-HPD compared to vehicle-ve hicle controls. However, striatal D-2 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 dens ity 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 constraints for D-2, 5-HT1A, and 5-HT2A recep tors were not affected by any treatment. These results suggest that di abetic state may affect brain serotonergic activity via an increase in the density of 5-HT2A receptors. This may indicate an increased vulne rability to major depression in patients with diabetes. The lack of an effect of the combined chronic treatment with STZ and HPD on the D-2 receptor density may correspond to the increased risk to develop tardi ve dyskinesia in patients with diabetes. (C) American College of Neuro psychopharmacology.