Upregulation of Striatal Dopamine-2 Receptors in Brattleboro Rats with Prepulse Inhibition Deficits

Background Brattleboro rats (BRATs) have natural deficits in prepulse inhibition (PPI) of the startle response similar to those exhibited by schizophrenia patients, which are reversed by antipsychotics. We sought to determine whether they also have increases in striatal dopamine-2 (D2) receptors found in some studies examining the brains of schizophrenia patients. Methods Several days after startle testing, the brains of BRAT and Long Evans (LE) rats were removed, and D1 and D2 receptor levels were measured by autoradiography. Results PPI was lower in BRATs consistent with previous reports. D2, but not D1, receptor binding was significantly higher in the nucleus accumbens shell and the dorsomedial caudate of BRAT compared with LE rats, consistent with some findings in schizophrenia patients. Furthermore, individual rat PPI was inversely correlated with D2 binding density. Conclusions These findings suggest that the dopamine system in BRATs is dysregulated and these abnormalities may contribute to the PPI deficits observed in these rats.