FURTHER-STUDIES ON THE RELATIONSHIP BETWEEN DOPAMINE CELL-DENSITY ANDHALOPERIDOL-INDUCED CATALEPSY

Previous data have suggested that the genetic variability in the sensi tivity to haloperidol-induced catalepsy is associated with the number of dopamine neurons in the substantia nigra zona compacta (SNZc). To f urther investigate this relationship, neuroleptic responsive (NR) and neuroleptic nonresponsive (NNR) lines were selected from the new heter ogeneous stock/Northport (Np). At the fourth selected generation (S-4) , the NR/Np and NNR/Np lines differed more than 5-fold in their halope ridol ED(50), but showed no difference in their ED(50) to SCH 23390. C onfirming the previous results, tyrosine hydroxylase (TH)-positive cel l number in the SNZc was significantly higher in the NNR/Np as compare d to the NR/Np line. The difference was most pronounced in the rostral SNZc, where TH cell number was increased 23%. Cell number also was in creased significantly (38%) in the caudal ventral tegmental area (VTA) . Fifty-two C57BL/6J:DBA/2J (B6D2) F-2 hybrids were phenotyped for hal operidol response before determination of TH cell number. Paralleling the results in the selected lines, TH cell number in the SNZc was sign ificantly (range, 10-28%) higher in the most nonresponsive F-2 hybrids . TH cell number was determined in the SNZc and VTA of 10 standard inb red mouse strains for which the ED(50) for haloperidol-induced catalep sy was known. TH cell number showed significant differences among inbr ed strains, with the largest difference (88%) noted between the 129/J and P/J strains in the rostral SNZc. In the VTA, differences as large as 95% were noted (AKR/crl vs. P/J). Among the inbred strains, there w as no significant relationship between cell number and response except in the medial SNZc, where the most responsive strains had the highest cell number. No significant correlations were found in the VTA. As no correlation between response and cell number in the inbred lines was found, this brings into question the validity of using genetic correla tions obtained from inbred strains to understand genetic relationships among outbred or hybrid populations.