The effects of the cholinergic immunotoxin 192 IgG-saporin (SAP) (0.0, 0.15, or 0.45 microg/microl; 0.5 microl/hemisphere) infused into the area of the nucleus basalis magnocellularis (NBM) of rats were tested in a five-choice serial reaction time task (5CSRTT) designed to assess visual attention. The effects of this manipulation on acetylcholine efflux in the medial frontal cortex were determined using in vivo microdialysis during the 5CSRTT. Rats with extensive lesions of the NBM (SAP HIGH) showed an array of behavioral deficits in the 5CSRTT hypothesized to represent deficits in central executive function that were associated with severe deficits in accuracy. Lengthening the stimulus duration ameliorated these deficits. Rats with restricted lesions of the NBM (SAP LOW) showed impairments over time on task when tested under standard conditions that were exacerbated by increases in the event rate. The number of choline acetyltransferase-immunoreactive cells in the area of the NBM but not the vertical limb of the diagonal band correlated significantly with accuracy in the task. SAP HIGH rats had significantly lower levels of cortical acetylcholine (ACh) efflux relative to SHAM both before and during the 5CSRTT. SAP LOW rats showed significantly higher levels of cortical ACh efflux before but not during the 5CSRTT. Cortical ACh efflux increased in all rats with the onset of the attentional task. These data provide the first direct evidence for a relationship between selective damage in the basal forebrain with decreased cortical ACh efflux and impaired attentional function.

The nucleus accumbens core (AcbC), anterior cingulate cortex (ACC), and central nucleus of the amygdala (CeA) are required for normal acquisition of tasks based on stimulus-reward associations. However, it is not known whether they are involved purely in the learning process or are required for behavioral expression of a learned response. Rats were trained preoperatively on a Pavlovian autoshaping task in which pairing a visual conditioned stimulus (CSϩ) with food causes subjects to approach the CSϩ while not approaching an unpaired stimulus (CSϪ). Subjects then received lesions of the AcbC, ACC, or CeA before being retested. AcbC lesions severely impaired performance; lesioned subjects approached the CSϩ significantly less often than controls, failing to discriminate between the CSϩ and CSϪ. ACC lesions also impaired performance but did not abolish discrimination entirely. CeA lesions had no effect on performance. Thus, the CeA is required for learning, but not expression, of a conditioned approach response, implying that it makes a specific contribution to the learning of stimulus-reward associations.Environmental stimuli that are associated with rewarding events thereby gain motivational significance through Pavlovian conditioning processes. Appetitive conditioned stimuli (CSs) have many properties, among which is the ability to attract attention and elicit approach (Hearst & Jenkins, 1974;Tomie, Brooks, & Zito, 1989). This conditioned approach response often has the beneficial function of drawing animals (including humans) closer to sources of natural rewards, such as food, but it may also play a detrimental role in attracting humans toward artificial reinforcers such as drugs of abuse, maintaining addiction and inducing relapse (Altman et al., 1996;Tiffany, 1990). For example, individuals with a propensity to form and respond to Pavlovian stimulus-reward associations have been suggested to be more vulnerable to addictive drugs (Tomie, 1996). It is therefore important to understand the neural mechanisms by which animals learn associations between stimuli and rewards, and the manner in which such associations control behavior.Autoshaping (Brown & Jenkins, 1968) is a measure of Pavlovian stimulus-reward learning in which subjects approach a CS that predicts reward. In a typical autoshaping task designed for use with rats , a visual stimulus (CSϩ) is presented on a computer screen and followed by delivery of food at a different location. A second stimulus (CSϪ) is also presented but never followed by food. Though the subject's behavior has no effect on food delivery, normal rats develop a conditioned response in which they selectively approach the food-predictive CS before returning to the food hopper to retrieve the primary reward. The autoshaped conditioned approach response is generally held to be under the control of Pavlovian, not instrumental, contingencies (Browne, 1976;Jenkins & Moore, 1973;Mackintosh, 1974;Williams & Williams, 1969), and this has been confirmed for the rat autoshaping task described .A...

These data are consistent with the hypothesis that isolation rearing produces enduring changes in the sensitivity of dopamine-mediated functions in amygdala-striatal circuitry that may be directly related to the altered reinforcing properties of cocaine and other psychomotor stimulants.

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