The Role of Dopamine Receptors in the Neurobehavioral Syndrome Provoked by Activation of L-Type Calcium Channels in Rodents

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Abstract
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 D3 or D1/5 dopamine receptor antagonists attenuated the behavioral effects of ±BayK 8644, while pretreatment with D2 or D4 antagonists had no effect. In D3 receptor knockout mice, ±BayK 8644 elicited both dystonia and self-biting, but these behaviors were less severe than in matched controls. In D1 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 D3 or D1/5 receptors.