THE NMDA RECEPTOR ANTAGONIST CPP SUPPRESSES LONG-TERM POTENTIATION INTHE RAT HIPPOCAMPAL-ACCUMBENS PATHWAY IN-VIVO

Excitation of afferent fibres originating in the ventral subiculum of the hippocampus through stimulation of the fimbria elicits field poten tials in the nucleus accumbens. When recorded in the dorsomedial aspec t of the nucleus accumbens, the evoked field responses consisted of an early, negative-going component (N1) 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 ac cumbens neurons; the N2 component appears to be polysynaptic in origin . In control rats, high-frequency stimulation of the fimbria (three tr ains at 250 Hz, 250 ms, delivered at 50 min intervals) resulted in a l ong-lasting potentiation of both the N1 and N2 components. The magnitu de of potentiation exhibited by the polysynaptic N2 response was typic ally greater than that of the monosynaptically evoked N1 response. Fol lowing delivery of the first train, the amplitude of the N1 and N2 com ponents was increased by similar to 20 and 50% respectively. Administr ation of the competitive N-methyl-D-aspartate (NMDA) receptor antagoni st (+/-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP, 10 mg /kg i.p.) had no significant effects on the evoked nucleus accumbens r esponses. High-frequency stimulation failed to produce a significant i ncrease in the amplitude of either the N1 or the N2 response when deli vered 45-60 min after CPP administration. To test whether the suppress ant effects of CPP were time-dependent, two further high-frequency tra ins were applied 90 and 180 min after administration of the drug. Sign ificant increases in the amplitude of the N1 and N2 components were ob served only after the third train, delivered 180 min after CPP injecti on. These results demonstrate that high-frequency stimulation of hippo campal afferents to the nucleus accumbens induces LTP in both a monosy naptic and a polysynaptic pathway. In both cases, the induction of LTP is suppressed in a time-dependent manner by the competitive NMDA rece ptor antagonist CPP. Thus, NMDA receptor activation appears to be prer equisite for the induction of LTP in the hippocampus - accumbens pathw ay.