LATENT INHIBITION - THE NUCLEUS-ACCUMBENS CONNECTION REVISITED

It has been proposed that dopaminergic transmission in the nucleus acc umbens plays a key role in regulating latent inhibition (LI), i.e. the retardation of conditioning that occurs if a to-be-conditioned stimul us is first presented a number of times ('preexposure') without other consequence. New evidence in support of this hypothesis is presented o r reviewed here, showing that: (1) intra-accumbens injection of halope ridol at the time of conditioning potentiates LI; (2) destruction of d opaminergic terminals in the nucleus accumbens potentiates LI; (3) int ra-accumbens haloperidol reverses the blockade of LI caused by systemi c nicotine; (4) intra-accumbens haloperidol reverses the blockade of L I caused by systemic amphetamine; (5) after a single systemic injectio n of amphetamine (insufficient on its own to block LI), a subsequent i ntra-accumbens injection of amphetamine at the time of conditioning bl ocks LI; and (6) intra-accumbens (like systemic) amphetamine administe red 15 min before conditioning, without prior systemic amphetamine, fa iled to block LI. The difference between the effects on LI of one and two administrations of amphetamine, respectively, is interpreted in te rms of the need for sensitisation of the response to amphetamine, with the result that the response to the second administration includes a component of impulse-dependent dopamine release in the nucleus accumbe ns that is otherwise lacking. Data from dialysis experiments suggest t hat such impulse-dependent accumbens dopamine release also occurs at r elatively long delays after a single systemic administration of amphet amine. It was accordingly predicted, and found, that, although LI is i ntact 15 min after an i.p. injection (confirming previous results), it is abolished at 90 min after the injection of amphetamine. This findi ng is consistent with the effects of amphetamine in human subjects, in whom LI is blocked 90 min after a single oral administration. Overall , these results strengthen the case that the blockade of LI by elevate d. and potentiation of LI by decreased, dopaminergic transmission are both due specifically to actions in the nucleus accumbens; and also ad d to the similarities between LI studied in animal and human subjects, respectively. (C) 1997 Elsevier Science B.V.