Nicotine ameliorates NMDA receptor antagonist-induced deficits in contextual fear conditioning through high-affinity nicotinic acetylcholine receptors in the hippocampus

摘要: NMDA glutamate receptors (NMDARs) and nicotinic acetylcholine (nAChRs) are both involved in learning synaptic plasticity. Increasing evidence suggests processes mediated by these may interact to modulate learning; however, little is known about the neural substrates interactive processes. The present studies investigated effects of nicotine on MK-801 hydrogen maleate (MK-801) DL-2-Amino-5-phosphonovaleric acid (APV)-induced disruption contextual fear conditioning male C57BL/6J mice, using direct drug infusion selective nAChR antagonists define brain regions subtypes involved. Mice treated with showed a deficit that was ameliorated nicotine. Direct demonstrated NMDAR disrupted hippocampal function acted dorsal hippocampus ameliorate learning. high-affinity antagonist Dihydro-β-erythroidine hydrobromide (DhβE) blocked MK-801-induced deficits while α7 methyllycaconitine citrate salt hydrate (MLA) did not. These results suggest NMDARs nAChRs mediate similar conditioning. Furthermore, have implications for developing effective therapeutics cognitive associated schizophrenia because large subset patients exhibit be related dysfunction smoke at much higher rates than healthy population, which an attempt deficits.