Two ideas have dominated the neuropsychology of the orbitofrontal cortex (OFC). One holds that OFC regulates emotion and enhances behavioral flexibility through inhibitory control. The other ascribes to OFC a role in updating valuations based on current motivational states. Neuroimaging, neurophysiological and clinical observations are consistent with either or both hypotheses. Although these hypotheses are compatible in principle, the present results support the latter view of OFC function and argue against the former. We show that excitotoxic, fibersparing lesions confined to OFC in monkeys do not alter either behavioral flexibility, as measured by object reversal learning, or emotion regulation, as assessed by snake fear. A follow-up experiment indicates that previous reports of a loss of inhibitory control resulted from damage to nearby fiber tracts and not from OFC dysfunction. Thus, OFC plays a more specialized role in reward-guided behavior and emotion than currently thought, a function that includes value updating.

Previous findings suggest that neuroadaptations downstream of D-1 dopamine (DA) receptor stimulation in nucleus accumbens (NAc) are involved in the enhancement of drug reward by chronic food restriction (FR). Given the high co-expression of D-1 and GluR1 AMPA receptors in NAc, and the regulation of GluR1 channel conductance and trafficking by D-1-linked intracellular signaling cascades, the present study examined effects of the D-1 agonist, SKF-82958, on NAc GluR1 phosphorylation, intracranial electrical self-stimulation reward (ICSS), and reversibility of reward effects by a polyamine GluR1 antagonist, 1-NA-spermine, in ad libitum fed (AL) and FR rats. Systemically administered SKF-82958, or brief ingestion of a 10% sucrose solution, increased NAc GluR1 phosphorylation on Ser845, but not Ser831, with a greater effect in FR than AL rats. Microinjection of SKF-82958 in NAc shell produced a reward-potentiating effect that was greater in FR than AL rats, and was reversed by co-injection of 1-NA-spermine. GluR1 abundance in whole cell and synaptosomal fractions of NAc did not differ between feeding groups, and microinjection of AMPA, while affecting ICSS, did not exert greater effects in FR than AL rats. These results suggest a role of NAc GluR1 in the reward-potentiating effect of D-1 DA receptor stimulation and its enhancement by FR. Moreover, GluR1 involvement appears to occur downstream of D-1 DA receptor stimulation rather than reflecting a basal increase in GluR1 expression or function. Based on evidence that phosphorylation of GluR1 on Ser845 primes synaptic strengthening, the present results may reflect a mechanism via which FR normally facilitates reward-related learning to re-align instrumental behavior with environmental contingencies under the pressure of negative energy balance.

Rationale-Previous studies have suggested that chronic food restriction (FR) increases sensitivity of a neural substrate for drug reward. The neuroanatomical site(s) of key neuroadaptations may include nucleus accumbens (NAc) where changes in D-1 dopamine (DA) receptor-mediated cell signaling and gene expression have been documented.Objectives-The purpose of the present study was to begin bridging the behavioral and tissue studies by microinjecting drugs directly into NAc medial shell and assessing behavioral effects in free-feeding and FR subjects.Materials and methods-Rats were implanted with microinjection cannulae in NAc medial shell and a subset were implanted with a stimulating electrode in lateral hypothalamus. Rewardpotentiating effects of the D-1 DA receptor agonist, SKF-82958, AMPAR antagonist, DNXQ, and polyamine GluR1 antagonist, 1-na spermine, were assessed using the curve-shift method of selfstimulation testing. Motor-activating effects of SKF-82958 were also assessed.Results-SKF-82958 (2.0 and 5.0 µg) produced greater reward-potentiating and motor-activating effects in FR than ad libitum fed (AL) rats. DNQX (1.0 µg) and 1-na spermine (1.0 and 2.5 µg) selectively decreased the x-axis intercept of rate-frequency curves in FR subjects, reflecting increased responding for previously subthreshold stimulation.Conclusions-Results suggest that FR may facilitate reward-directed behavior via multiple neuroadaptations in NAc medial shell including upregulation of D-1 DA receptor function involved in the selection and expression of goal-directed behavior, and increased GluR1-mediated activation of cells that inhibit nonreinforced responses.

It is widely accepted that the amygdala plays a critical role in acquisition and consolidation of fear-related memories. Some of the more widely employed behavioral paradigms that have assisted in solidifying the amygdala's role in fear-related memories are associative learning paradigms. With most associative learning tasks, a neutral conditioned stimulus (CS) is paired with a salient unconditioned stimulus (US) that elicits an unconditioned response (UR). After multiple CS-US pairings, the subject learns that the CS predicts the onset or delivery of the US, and thus elicits a learned conditioned response (CR). Most fear-related associative paradigms have suggested that an aspect of the fear association is stored in the amygdala; however, some fear-motivated associative paradigms suggest that the amygdala is not a site of storage, but rather facilitates consolidation in other brain regions. Based upon various learning theories, one of the most likely sites for storage of long-term memories is the neocortex. In support of these theories, findings from our laboratory, and others, have demonstrated that trace-conditioning, an associative paradigm where there is a separation in time between the CS and US, induces learning-specific neocortical plasticity. The following review will discuss the amygdala's involvement, either as a site of storage or facilitating storage in other brain regions such as the neocortex, in fear- and non-fear-motivated associative paradigms. In this review, we will discuss recent findings suggesting a broader role for the amygdala in increasing the saliency of behaviorally relevant information, thus facilitating acquisition for all forms of memory, both fear- and non-fear-related. This proposed promiscuous role of the amygdala in facilitating acquisition for all memories further suggests a potential role of the amygdala in general learning disabilities.