Iminodipropionitrile‐Induced Dyskinesia in Mice: Striatal Calcium Channel Changes and Sensitivity to Calcium Channel Antagonists

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Abstract
Administration of 3, 3′‐iminodipropionitrile (IDPN) (1g/kg, i.p. for 3 days) in mice leads to the development of a characteristic syndrome consisting of lateral and vertical head and neck movements, hyperactivity, random circling, increased locomotor activity, and increased startle response. Nifedipine, verapamil, and diltiazem (10 mg/kg) inhibited significantly the symptoms of IDPN‐induced dyskinesia. However, there was no change in the affinity (KD) or the density of PN 200–110 binding sites (Bmax) in whole brains of IDPN‐treated mice. Similarly, the K+‐depolarization‐dependent Ca2+ uptake in synaptosomes from whole brain, cortex, or striatum was not altered following IDPN treatment. However, IDPN caused a significant increase in the Bmax value (from 157 ± 7 fmol/mg to 237 ± 31 fmol/mg in control and treated groups, respectively) of PN 200–110 binding to the striatum without change of KD value (38 ± 4.7 pM versus 33 ± 1.6 pM). IDPN also caused a slight but significant decrease in the KD value (from 68 ± 10.1 pM to 45 ± 4.5 pM in control and treated groups, respectively), without significant change of Bmax value (563 ± 51 fmol/mg versus 485 ± 41 fmol/mg) of PN 200–110 binding to the cortex. IDPN did not alter ω‐conotoxin binding in whole brain, striatum, or cortex. The behavioral effects of chronic IDPN treatment are inhibited by L‐type calcium channel antagonists and this may be associated with the observed increase in striatal L‐type calcium channels.

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