PMID: 8968368Dec 1, 1996Paper

Genetics, neuroleptic response and the organization of cholinergic neurons in the mouse striatum

The Journal of Pharmacology and Experimental Therapeutics
K DainsR Hitzemann

Abstract

Compared with the neuroleptic nonresponsive (NNR) mouse line, the neuroleptic responsive (NR) line has a significantly higher number of striatal cholinergic neurons (Hitzemann et al., 1993). We now report additional information on this genetic association. At the fifth selected generation, a new selection of the NR and NNR lines differed 5-fold in their ED50 values (1 vs. 5 mg/kg) for haloperidol-induced catalepsy and 20% in the number of striatal cholinergic neurons (higher in the NR line). This association was further examined in 10 standard inbred mouse strains; eight of the strains had been crossed to form the heterogeneous stock from which the new NR and NNR lines were selected. In this panel, we detected no significant association between number of cholinergic neurons and haloperidol response. To examine the similarities and differences in the modes of inheritance for the two phenotypes, we formed a full Mendelian cross from the C57BL/6 (B6) and DBA/2 (D2) mouse strains. The B6 and D2 strains differ 9-fold in their haloperidol ED50 values (3.9 vs. 0.4 mg/kg) and more than 30% in the number of cholinergic neurons (higher in the D2 strain). Haloperidol-induced catalepsy was described by a simple additive genetic model; the ...Continue Reading

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