Altered responses to novelty and drug reinforcement in adult rats treated neonatally with domoic acid

Abstract Activity in the mesocorticolimbic dopamine system is linked to responses to novelty, reward, and drug-seeking behaviours. Glutamate signaling, through kainate receptors, has been shown to modulate dopamine release in this pathway. In the present study, a low, overtly non-convulsive dose of the kainate receptor agonist, domoic acid (DOM), was administered to rat pups over PND 8–14. As juveniles and adolescents, rats were assessed in the open field. During adulthood, rats were tested in an open field, a sucrose consumption task, the playground maze and in a nicotine-induced conditioned place preference paradigm. Domoic acid related effects were found in open field behavior at each time point assessed. Male rats treated neonatally with DOM displayed altered novelty-related behaviour in a novelty trial, as indicated by an increase in time spent exploring familiar objects during the novelty trial of the playground maze. In nicotine-induced conditioned place preference, DOM-treated females developed a conditioned place preference for the nicotine-paired compartment of the test arena, an effect that was maintained for at least a month following the final drug-compartment pairing. The results of this study underscore the importance of the glutamate system in the ontogeny of behaviors that rely on the functional integrity of the midbrain dopamine system.