The L-type calcium channel blocker nifedipine impairs extinction, but not reduced contingency effects, in mice.
We recently reported that fear extinction, a form of inhibitory learning, is selectively blocked by systemic administration of L-type voltage-gated calcium channel (LVGCC) antagonists, including nifedipine, in mice. We here replicate this finding and examine three reduced contingency effects after vehicle or nifedipine (40 mg/kg) administration. In the first experiment, contingency reduction was achieved by adding USs to the training protocol (degraded contingency), a phenomenon thought to be independent of behavioral inhibition. In the second experiment, contingency reduction was achieved by varying the percentage of CS-US pairing, a phenomenon thought to be weakly dependent on behavioral inhibition. In the third and fourth experiments, contingency reduction was achieved by adding CSs to the training protocol (partial reinforcement), a phenomenon thought to be completely dependent on behavioral inhibition. We found that none of these reduced contingency effects was impaired by nifedipine. In a final experiment, we found that extinction conducted 1 or 3 h post-acquisition, but not immediately, was LVGCC-dependent. Taken together, the results suggest that reduced contingency effects and extinction depend on different molecular mechanisms and that LVGCC dependence of behavioral inhibition develops with time after associative CS-US learning.
Cain
Christopher K
CK
Interdepartmental Program in Neuroscience, University of California Los Angeles, Los Angeles, California 90095-1761, USA.
Godsil
Bill P
BP
Jami
Shekib
S
Barad
Mark
M
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D003216:Conditioning, Operant / Q000187:drug effects*; D003463:Cues; D005108:Extinction, Psychological / Q000187:drug effects*; D005239:Fear / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009543:Nifedipine / Q000494:pharmacology*; D012055:Reinforcement Schedule
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D009543:Nifedipine