NMDA, But Not Dopamine D₂, Receptors in the Rat Nucleus Accumbens Are Involved in Guidance of Instrumental Behavior by Stimuli Predicting Reward Magnitude

Abstract

Expectancy of future reward is an important factor guiding the speed of instrumental behavior. The present study sought to explore whether signals transmitted via the NMDA subtype of glutamate receptors and via dopamine D 2 receptors in the nucleus accumbens (NAc) are critical for the determination of reaction times (RTs) of instrumental responses by the expectancy of future reward. A simple RT task for rats demanding conditioned lever release was used in which the upcoming reward magnitude (5 or 1 pellet) was signaled in advance by discriminative stimuli. In trained rats, RTs of conditioned responses with expectancy of a high reward magnitude were found to be significantly shorter. The shortening of RTs by stimuli predictive of high reward to be obtained was dose-dependently impaired by bilateral intra-NAc infusion of the competitive NMDA antagonist DL-2-amino-5-phosphonovaleric acid (APV) (1, 2, or 10 g in 0.5 l/side), but not by infusion of the preferential dopamine D 2 antagonist haloperidol (5 and 12.5 g in 0.5 l/side) or by infusion of vehicle (0.5 l/side). In conclusion, the data reveal that in well trained animals stimulation of intra-NAc NMDA, but not of dopamine D 2 , receptors, is critically involved in guiding the speed of instrumental responses according to stimuli predictive of the upcoming reward magnitude.Key words: nucleus accumbens; goal-directed behavior; reward; dopamine; glutamate; reaction time; rat Reward expectancy is an important factor of guidance in adaptive motor behavior. Accordingly, the speed of instrumental responses has been found to be a function of the expected reward magnitude because reaction times (RTs) of rats were shortened by expectancy of signaled high reward (Brown and Bowman, 1995). Likewise, RTs of reaching movements (Hollerman et al., 1998) or saccadic eye movements (Kawagoe et al., 1998) of primates decreased as a function of the relative attractiveness of the expected reward.The nucleus accumbens (NAc) as an interface between limbic and motor structures (Groenewegen et al., 1996) may play a key role in the control of goal-directed actions by reward (Mogenson et al., 1980). It is generally assumed that the NAc subserves motivated behaviors such as feeding, sexual behavior, or exploratory locomotion elicited by primary reward and by conditioned stimuli associated with reward Everitt, 1990;Mitchell and Gratton, 1994;Watanabe, 1996). For instance, lesions of the NAc abolished conditioned place preference (Everitt et al., 1991), suggesting that environmental cues predictive for reward no longer control behavior. Furthermore, neurons in the striatum show reward expectation-related activations triggered by reward-predicting stimuli (Apicella et al., 1991;Schultz et al., 1992;Kawagoe et al., 1998). Depending on the expected type of reinforcer, behaviorrelated neuronal activity of striatal neurons is influenced differentially, implying that these neurons incorporate information about the expected behavioral outcome (Hollerman et al., 1998). Although these data suggest that ...

Differential Effects of Nucleus Accumbens Core, Shell, or Dorsal Striatal Inactivations on the Persistence, Reacquisition, or Reinstatement of Responding for a Drug-Paired Conditioned Reinforcer

“…This suggests that the DStr is involved more specifically with responding for the conditioned reinforcer, while the NAcc core may mediate some of the activational or discriminative aspects of behavioral control during acquisition of an instrumental response. Indeed, blockade of glutamate receptors in the NAcc core attenuated the acquisition of instrumental responding (Kelley et al, 1997), and discriminative control over responding (Hauber et al, 2000;. In the present study, inactivation of the NAcc core decreased discriminated responding, as changes in lever presses were the same for presses on both the active and inactive levers.…”

Isotropic sequence order learning using a novel linear algorithm in a closed loop behavioural system

“…Thus, our model needs only one neuronal circuit whereas the TD model needs two: one for the prediction and one for the error. Either models are supported by biology: for example the TD model is supported by results from Schultz et al (1997) and the model presented here by Hauber et al (2001). Another biological aspect is the weight change curve in our model which is reminiscent of the spike-timing dependent plasticity curves which show the change of synaptic potentials observed during long-term potentiation or depression in physiological paired-pulse experiments (Bi and Poo, 1998;Markram et al, 1997).…”

Dissociable Effects of Antagonism of NMDA and AMPA/KA Receptors in the Nucleus Accumbens Core and Shell on Cocaine-seeking Behavior

“…In a recent study that compared reaction times of responses for reward in the presence of stimuli predictive of different reward magnitudes, reaction times were shorter in the presence of stimuli predictive of high, than in the presence of stimuli predictive of lower, reward. Infusion of AP-5 into the NAcc, in the region of the core, impaired the shortening of reaction-times normally seen in rats expecting high reward (Hauber et al 2000). Together, these studies suggest a critical role for the core and its afferents in appetitive behavior under the control of reward-associated stimuli.…”

“…Indeed, recent data suggest that NMDA receptors in the NAcc core may subserve a general motivational role. For example, intra-core infusions of NMDA receptor antagonists abolished the reduction in reaction time to respond for stimuli predictive of high reward magnitude, as compared to the reaction time to respond for cues predictive of smaller rewards (Hauber et al 2000).…”