The role of dopamine receptors in the neurobehavioral syndrome provoked by activation of L-type calcium channels in rodents.
In rodents, activation of L-type calcium channels with +/-BayK 8644 causes an unusual behavioral syndrome that includes dystonia and self-biting. Prior studies have linked both of these behaviors to dysfunction of dopaminergic transmission in the striatum. The current studies were designed to further elucidate the relationship between +/-BayK 8644 and dopaminergic transmission in the expression of the behavioral syndrome. The drug does not appear to release presynaptic dopamine stores, since microdialysis of the striatum revealed dopamine release was unaltered by +/-BayK 8644. In addition, the behaviors were preserved or even exaggerated in mice or rats with virtually complete dopamine depletion. On the other hand, pretreatment of mice with D(3) or D(1/5) dopamine receptor antagonists attenuated the behavioral effects of +/-BayK 8644, while pretreatment with D(2) or D(4) antagonists had no effect. In D(3) receptor knockout mice, +/-BayK 8644 elicited both dystonia and self-biting, but these behaviors were less severe than in matched controls. In D(1) receptor knockout mice, behavioral responses to +/-BayK 8644 appeared exaggerated. These results argue that the behavioral effects of +/-BayK 8644 are not mediated by a presynaptic influence. Instead, the behaviors appear to result from a postsynaptic activation of the drug, which does not require but can be modified by D(3) or D(1/5) receptors.
Kasim
Suhail
S
Department of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA.
Blake
Bonita L
BL
Fan
Xueliang
X
Chartoff
Elena
E
Egami
Kiyoshi
K
Breese
George R
GR
Hess
Ellen J
EJ
Jinnah
H A
HA
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D004421:Dystonia / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D016728:Self-Injurious Behavior / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D013570:Synaptic Membranes / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013577:Syndrome
D002120:Calcium Channel Agonists; D020746:Calcium Channels, L-Type; D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D050637:Receptors, Dopamine D3; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D004298:Dopamine