Pharmacogenetics of cocaine: II. Mesocorticolimbic and striatal dopamine and cocaine receptors in C57BL and DBA mice

Polymorphisms in the dopamine D2 receptor gene and their relationships to striatal dopamine receptor density of healthy volunteers

“…Differences in dopamine D2 receptor-binding characteristics between different inbred mice and rat strains have been repeatedly confirmed. [16][17][18][19][20][21][22][23][24] In inbred mice strains a genome-wide search for catalepsy-related genes using a quantitative trait loci approach detected a locus near or at the DRD2.25 Therefore, also in humans several attempts have been performed searching for associations between dopamine D2 receptor polymorphisms and different measures of dopaminergic binding parameters or glucose metabolism in brain regions containing dopaminergic innervation (Table 1).In a recent PET investigation of Finnish healthy individuals the DRD2 TaqIA1 allele, suggested to be connected with alcoholism, 26 was associated with reduced striatal D2 receptor availability.3 So far there is no evidence that the DRD2 TaqIA polymorphism has a functional role. It has rather been assumed that the relationships obtained between the DRD2 TaqIA polymorphism and phenotype data are due to linkage disequilibrium between the DRD2 TaqIA polymorphism and another adjacent functional polymorphism.…”

“…Differences in dopamine D2 receptor-binding characteristics between different inbred mice and rat strains have been repeatedly confirmed. [16][17][18][19][20][21][22][23][24] In inbred mice strains a genome-wide search for catalepsy-related genes using a quantitative trait loci approach detected a locus near or at the DRD2. 25 Therefore, also in humans several attempts have been performed searching for associations between dopamine D2 receptor polymorphisms and different measures of dopaminergic binding parameters or glucose metabolism in brain regions containing dopaminergic innervation (Table 1).…”

Steps to a neurochemistry of personality

“…Variation in NAS DA release may be the result of strain-dependent differences in DA D 2 , but not D 1 , receptor densities. Increased density of D 2 autoreceptors located on VTA neurons, and lower D 2 postsynaptic receptors in the NAS, were observed in DBA relative to C57 mice (Erwin et al 1993;Kanes et al 1993;Ng et al 1994;Puglisi-Allegra et al 1994). Activation of D 2 autoreceptors inhibits impulse flow, synthesis, and release rates of DA neurons (White & Wang 1984), and D 2 autoreceptors have higher affinity relative to postsynatic DA receptors for DA and DA agonists (Bannon et al 1980;Skirboll et al 1978).…”

The regulation of D2 dopamine receptor expression

“…Receptor density in the BALB/cJ strain was 60-80% higher than in the DBA strain. Subsequent studies [40][41][42][43][44] have confirmed that there is a marked difference in receptor density among inbred mouse strains. However, it is important to note that the relative difference among strains depends on the region examined.…”

“…However, it is important to note that the relative difference among strains depends on the region examined. For example, the C57 strain has a higher receptor density than the DBA strain in the striatum 43,44 but a lower receptor density in the substantia nigra and ventral tegmental area; 44 the latter difference in part is related to a higher number of midbrain dopamine neurons in the DBA strain. 45 Differences in receptor density have also been found among inbred rat strains in some [46][47][48] but not all studies.…”