Correlated asymmetries in striatal D1 and D2 binding: relationship to apomorphine-induced rotation.
Long-Evans derived rats were tested for nocturnal, amphetamine-induced and apomorphine-induced rotation (circling behavior); the rats' left and right striata were subsequently dissected and D1 and D2 receptor densities (Bmax) were assayed in the same striatal homogenates using [3H]SCH-23390 and [3H]N-methylspiperone, respectively. D1 and D2 Bmax values were correlated (r = 0.68). Moreover, left-right asymmetries in D1 and D2 Bmax values were more highly correlated (r = 0.84). Although asymmetries in D1 and D2 binding were not by themselves related to rotational behavior, an asymmetry in the ratio or balance of D1 and D2 binding was associated with the direction of apomorphine-induced rotation: the D1/D2 ratio of Bmax values was significantly higher in the striatum ipsilateral to the preferred direction of apomorphine-induced rotation. These results suggest that normal variations in numbers of D1 and D2 receptors are determined by a common mechanism, that D1 and D2 receptors are functionally coupled, and that, with respect to activation of striatal receptors, D1 is inhibitory and D2 is excitatory. The effects of apomorphine, a mixed D1 and D2 agonist, appear to reflect the balance between D1 and D2 receptors.
Glick
S D
SD
Department of Pharmacology and Toxicology, Albany Medical College, NY 12208.
Lyon
R A
RA
Hinds
P A
PA
Sowek
C
C
Titeler
M
M
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D002940:Circadian Rhythm; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003913:Dextroamphetamine / Q000494:pharmacology; D007839:Functional Laterality; D007700:Kinetics; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012016:Reference Values; D013239:Stereotyped Behavior / Q000187:drug effects*
D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D001058:Apomorphine; D003913:Dextroamphetamine