Dopamine receptor binding in inbred mice: strain differences in mesolimbic and nigrostriatal dopamine binding sites.

Abstract

Dopamine receptors were examined by Scatchard analysis in the striatal and olfactory tubercle regions of 11 inbred mouse strains. Simultaneous determinations of the binding characteristics of 3H-labeled 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN), a dopaminergic agonist and [3H]spiroperidol, a dopaminergic antagonist, were examined. Among the 11 strains, the equilibrium dissociation constant (Kd) for agonist binding did not vary in either the striatum or the olfactory tubercle. No strain differences were observed in the Kd for spiroperidol in either region, although the Kd for spiroperidol in the olfactory tubercle was uniformly higher than that in the striatum. Measurement of receptor concentrations revealed strain differences of up to 2-fold for both [3H]ADTN and [3H]spiroperidol binding sites. Within each brain region, the densities of agonist and antagonist binding sites correlated significantly. Between brain regions there was no correlation in the density of agonist or antagonist binding sites, which suggests that mesolimbic and nigrostriatal dopamine neurons may be under independent genetic control. Analysis of [3H]spiroperidol displacement by clofluperol, aceperone, cinanserin and mianserin in 4 inbred mouse strains revealed that 88-90% of the striatal sprioperidol sites are dopaminergic, with the remainder being serotonergic. Of the olfactory tubercle [3H]spiroperidol binding sites 53-66% are dopaminergic and 34-47% are serotonergic. Genetic differences in serotonin receptors and dopamine receptors may exist among inbred mouse strains.