Iminodipropionitrile-induced dyskinesia in mice: striatal calcium channel changes and sensitivity to calcium channel antagonists.
Administration of 3,3'-iminodipropionitrile (IDPN) (1 g/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 omega-conotoxin binding in whole brain, striatum, or cortex. The behavioral effects of chronic IDPN treatment as inhibited by L-type calcium channel antagonists and this may be associated with the observed increase in striatal L-type calcium channels.
Bangalore
R
R
Department of Biochemical Pharmacology, School of Pharmacy, State University of New York, Buffalo 14260.
Hawthorn
M
M
Triggle
D J
DJ
D000818:Animals; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000378:metabolism / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D017275:Isradipine; D008297:Male; D051379:Mice; D009570:Nitriles / Q000494:pharmacology*; D010069:Oxadiazoles / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D009570:Nitriles; D010069:Oxadiazoles; C008110:3,3'-iminodipropionitrile; D002118:Calcium; D017275:Isradipine