Modulation of latent inhibition in the rat by altered dopamine transmission in the nucleus accumbens at the time of conditioning

Latent inhibition describes a process by which pre-exposure of a stimulus w ithout consequence retards the learning of subsequent conditioned associati ons with that stimulus. It is well established that latent inhibition in ra ts is impaired by increased dopamine function and potentiated by reduced do pamine function. Previous evidence has suggested that these effects are mod ulated via the meso-accumbens dopamine projections. We have now undertaken three experiments to examine this issue directly, especially in the light o f one study in which latent inhibition was reported to be unaffected by dir ect injection of amphetamine into the accumbens. Latent inhibition was stud ied using the effect of pre-exposure of a tone stimulus on the subsequent f ormation of a conditioned emotional response to the tone. 6-Hydroxydopamine -induced lesions of dopamine terminals in the nucleus accumbens resulted in potentiation of latent inhibition. Bilateral local injections of the dopam ine antagonist haloperidol into the nucleus accumbens (0.5 mug/side) before conditioning also potentiated latent inhibition. Moreover, such injections were able to reverse the disruptive effect of systemic amphetamine (1 mg/k g, i.p.) on latent inhibition. Bilateral local injection of amphetamine (5 mug/side) into the nucleus accumbens before conditioning was able to disrup t latent inhibition, provided that it was preceded by a systemic injection of amphetamine (1 mg/kg) 24 h earlier. We conclude that the attenuation of latent inhibition by increased dopamine function in the nucleus accumbens is brought about by impulse-dependent re lease of the neurotransmitter ocurring at the time of conditioning. The pre viously reported failure to disrupt latent inhibition with intra-accumbens amphetamine is probably due to impulse-independent release of dopamine. The implications of these conclusions for theories linking disrupted latent in hibition to the attentional deficits in schizophrenia, and to the dopamine theory of this disorder, are discussed. (C) 2000 IBRO. Published by Elsevie r Science Ltd. All rights reserved.