Ia. Sukhotina et al., Effects of calcium channel blockers on behaviors induced by the N-methyl-D-aspartate receptor antagonist, dizocilpine, in rats, PHARM BIO B, 63(4), 1999, pp. 569-580
The present study assessed the ability of voltage-sensitive calcium channel
(VSCC) blockers to affect the behavioral effects of the noncompetitive N-m
ethyl-D-aspartate (NMDA) receptor antagonist, dizocilpine, in male Wistar r
ats. Dizocilpine produced dose-dependent increases in locomotor activity. N
imodipine, verapamil, and flunarizine suppressed dizocilpine-facilitated ve
rtical activity, while horizontal activity was attenuated by verapamil and
nimodipine but not flunarizine. Repeated dizocilpine injections resulted in
the development of sensitization to its locomotor stimulating properties.
Development of sensitization was not context specific, and was observed fol
lowing repeated exposures to 0.1 but not 0.056 or 0.3 mg/kg of dizocilpine.
Nimodipine retarded the development of sensitization to dizocilpine's stim
ulating effects on horizontal activity, while verapamil suppressed sensitiz
ation to the vertical stimulating effects of dizocilpine. Flunarizine had n
o significant effects on sensitization to dizocilpine's locomotor stimulati
ng properties. In rats trained to discriminate between injections of 0.056
mg/kg of dizocilpine and vehicle, none of the tested VSCC blockers was able
to completely antagonize the discriminative stimulus properties of dizocil
pine. Nimodipine, when administered in combination with the training dose o
f dizocilpine, modestly decreased the dizocilpine-lever selection. Dizocilp
ine dose dependently decreased the self-determined stimulation threshold im
planted in rats with electrodes into the ventral tegmental area. Nimodipine
exhibited some tendency to block the facilitating effects of dizocilpine,
while verapamil and flunarizine had no effects. In summary, in the present
experiments VSCC blockers exerted only modest interactions with the behavio
ral effects of dizocilpine, and it is unlikely that VSCC blockers have rema
rkable potential as adjunct treatment aimed at correcting the negative side
effects of NMDA receptor antagonists (e.g., dizocilpine). (C) 1999 Elsevie
r Science Inc.