Dopamine and acetylcholine cell density in the neuroleptic responsive (NR) and neuroleptic nonresponsive (NNR) lines of mice

The neuroleptic responsive (NR) and neuroleptic nonresponsive (NNR) selected lines of mice differ more than 10-fold in the ED₅₀ for catalepsy induced by a wide variety of neuroleptics with a high dopamine D₂/D₁ receptor activity ratio, e.g., haloperidol. The NR and NNR lines also differ significantly in dopamine D₂ somatodendritic receptor density; within the substantia nigra zona compacta and the ventral tegmental area, the increases in the NNR line are on average 33 and 48%, respectively. We now report that the NNR line has a higher number of dopamine neurons in the midrostral to the midcaudal aspect of the substantia nigra zona compacta. Within this region, the increase in dopamine cell number was on average 41%. In contrast to these data, there was no difference in cell number between lines in the ventral tegmental area. Thus, the increase of midbrain dopamine D₂ receptor density in the NNR line can only be accounted for in part by an increase in the number of dopamine neurons. Although the number of dopamine neurons in the substantia nigra zona compacta was increased in the NNR line, the density of dopamine terminals in the caudate-putamen as estimated by the [³H] mazindol technique was modestly but significantly higher (8%) in the NR line. The selected lines also differed within the caudate-putamen in the number of cholinergic neurons. The NR line had a significantly higher number of cholinergic neurons in the rostral caudate-putamen. Overall, these data illustrate that selective breeding for neuroleptic response has yielded lines of mice with significant differences in both the cholinergic and dopaminergic systems of the basal ganglia.