title: Modulation of latent inhibition in the rat by altered dopamine transmission in the nucleus accumbens at the time of conditioning.
abstract: Latent inhibition describes a process by which pre-exposure of a stimulus without consequence retards the learning of subsequent conditioned associations with that stimulus. It is well established that latent inhibition in rats is impaired by increased dopamine function and potentiated by reduced dopamine function. Previous evidence has suggested that these effects are modulated via the meso-accumbens dopamine projections. We have now undertaken three experiments to examine this issue directly, especially in the light of one study in which latent inhibition was reported to be unaffected by direct injection of amphetamine into the accumbens. Latent inhibition was studied using the effect of pre-exposure of a tone stimulus on the subsequent formation 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 dopamine antagonist haloperidol into the nucleus accumbens (0.5 microg/side) before conditioning also potentiated latent inhibition. Moreover, such injections were able to reverse the disruptive effect of systemic amphetamine (1mg/kg, i.p.) on latent inhibition. Bilateral local injection of amphetamine (5 microg/side) into the nucleus accumbens before conditioning was able to disrupt latent inhibition, provided that it was preceded by a systemic injection of amphetamine (1mg/kg) 24h earlier.We conclude that the attenuation of latent inhibition by increased dopamine function in the nucleus accumbens is brought about by impulse-dependent release of the neurotransmitter occurring at the time of conditioning. The previously 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 inhibition to the attentional deficits in schizophrenia, and to the dopamine theory of this disorder, are discussed.
authors: MRC Behavioural Neurochemistry Group and Department of Psychology, Institute of Psychiatry, Denmark Hill, SE5 8AF, London, UK. mhj1@le.ac.uk
authors: M H
authors: MH
authors: Joseph
authors: S L
authors: SL
authors: Peters
authors: P M
authors: PM
authors: Moran
authors: G A
authors: GA
authors: Grigoryan
authors: A M
authors: AM
authors: Young
authors: J A
authors: JA
authors: Gray
mesh_terms: D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001245:Association Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001927:Brain Diseases / Q000139:chemically induced / Q000503:physiopathology / Q000523:psychology; D003213:Conditioning, Psychological / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D007267:Injections; D007274:Injections, Intraperitoneal; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D016627:Oxidopamine; D000661:Amphetamine; D006220:Haloperidol; D004298:Dopamine