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Facilitation of shuttle-box avoidance behaviour in mice treated with nifedipine in combination with amphetamine
J Vetulani1, M Battaglia, C Castellano
1Istituto di Psicobiologia e Psicofarmacologia, CNR, Roma, Italy.
Abstract:
The dihydropyridine calcium channel antagonist nifedipine, tested in mice of CD-1, C57BL/6 and DBA/2 strains, at doses of 2.5, 5 and 10 mg/kg IP, had no significant effect on shuttle-box avoidance acquisition. Nifedipine also failed to affect performance retention in CD-1 mice subjected to a one-trial passive avoidance task (step-through). While ineffective alone, nifedipine strongly enhanced the shuttle-box avoidance facilitating action of amphetamine (1 and 2 mg/kg IP) in low performing CD-1 mice. The results indicate that although calcium channel blockers do not affect learning in avoidance paradigms in normal animals, they can interfere with the effects of other centrally acting drugs. Calcium antagonists might interfere with neuronal changes induced by amphetamine, but at present it is difficult to explain the strong avoidance facilitation produced by combinations of nifedipine and amphetamine. A possibility that the action of nifedipine on cerebral circulation is involved in the amphetamine-nifedipine interaction cannot be excluded.
Insights
Nifedipine, a calcium channel blocker, did not impact learning in mice. However, it significantly amplified amphetamine's learning-enhancing effects in a specific avoidance task.
Area of Science:
- Neuropharmacology
- Behavioral Neuroscience
Background:
- Calcium channel blockers are crucial in cardiovascular medicine.
- Their effects on cognitive functions, particularly learning and memory, remain an area of active research.
- Nifedipine is a dihydropyridine calcium channel antagonist with known central nervous system effects.
Purpose of the Study:
- To investigate the effects of nifedipine on learning and memory in mice using established behavioral paradigms.
- To determine if nifedipine modulates the effects of amphetamine, a known cognitive enhancer, on learning.
Main Methods:
- Nifedipine was administered to mice (CD-1, C57BL/6, DBA/2 strains) at varying doses (2.5, 5, 10 mg/kg IP).
- Behavioral tasks included shuttle-box avoidance acquisition and a one-trial passive avoidance task (step-through).
- Interactions between nifedipine and amphetamine (1 and 2 mg/kg IP) were assessed in low-performing CD-1 mice.
Main Results:
- Nifedipine alone did not significantly affect avoidance acquisition or passive avoidance retention in mice.
- Nifedipine markedly potentiated the avoidance-facilitating effects of amphetamine in CD-1 mice.
- No significant effects were observed when nifedipine was administered alone.
Conclusions:
- Calcium channel blockers like nifedipine do not impair learning in standard avoidance tasks in normal animals.
- Nifedipine can significantly alter the behavioral effects of other centrally acting drugs, such as amphetamine.
- The mechanism underlying the synergistic enhancement of avoidance learning by nifedipine and amphetamine requires further investigation, potentially involving cerebral circulation effects.
