The NMDA Receptor Antagonist CPP Suppresses Long‐term Potentiation in the Rat Hippocampal — accumbens PathwayIn Vivo

K. J. Feasey‐Truger; G. Ten Bruggencate

摘要

AbstractExcitation of afferent fibres originating in the ventral subiculum of the hippocampus through stimulation of the fimbria elicits field potentials in the nucleus accumbens. When recorded in the dorsomedial aspect of the nucleus accumbens, the evoked field responses consisted of an early, negative‐going component (Nl) with a peak latency of 8–10 ms, followed by a second negative‐going peak (N2) with a latency of 22–24 ms. The N1 response reflects monosynaptic activation of nucleus accumbens neurons; the N2 component appears to be polysynaptic in origin. In control rats, high‐frequency stimulation of the fimbria (three trains at 250 Hz, 250 ms, delivered at 50 min intervals) resulted in a long‐lasting potentiation of both the N1 and N2 components. The magnitude of potentiation exhibited by the polysynaptic N2 response was typically greater than that of the monosynaptically evoked N1 response. Following delivery of the first train, the amplitude of the N1 and N2 components was increased by ‐20 and 50 respectively. Administration of the competitiveN‐methyl‐d‐aspartate (NMDA) receptor antagonist 3‐(±)‐2‐carboxypiperazin‐4‐yl‐propyl‐1‐phosphonic acid (CPP, 10 mg/kg i.p.) had no significant effects on the evoked nucleus accumbens responses. High‐frequency stimulation failed to produce a significant increase in the amplitude of either the N1 or the N2 response when delivered 45–60 min after CPP administration. To test whether the suppressant effects of CPP were time‐dependent, two further high‐frequency trains were applied 90 and 180 min after administration of the drug. Significant increases in the amplitude of the N1 and N2 components were observed only after the third train, delivered 180 min after CPP injection. These results demonstrate that high‐frequency stimulation of hippocampal afferents to the nucleus accumbens induces LTP in both a monosynaptic and a polysynaptic pathway. In both cases, the induction of LTP is suppressed in a time‐dependent manner by the competitive NMDA receptor antagonist CPP. Thus, NMDA receptor activation appears to be prerequisite for the inducti

The NMDA Receptor Antagonist CPP Suppresses Long‐term Potentiation in the Rat Hippocampal — accumbens PathwayIn Vivo

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