Roles of nucleus accumbens and basolateral amygdala in autoshaped lever pressing

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Abstract

Initially-neutral cues paired with rewards are thought to acquire motivational significance, as if the incentive motivational value of the reward is transferred to the cue. Such cues may serve as secondary reinforcers to establish new learning, modulate the performance of instrumental action (Pavlovian-instrumental transfer, PIT), and be the targets of approach and other cue-directed behaviors. Here we examined the effects of lesions of the ventral striatal nucleus accumbens (ACb) and the basolateral amygdala (BLA) on the acquisition of discriminative autoshaped lever-pressing in rats. Insertion of one lever into the experimental chamber was reinforced by sucrose delivery, but insertion of another lever was not reinforced. Although sucrose was delivered independently of the rats’ behavior, sham-lesioned rats rapidly came to press the reinforced but not the nonreinforced lever. Bilateral ACb lesions impaired the initial acquisition of sign-tracking but not its terminal levels. In contrast, BLA lesions produced substantial deficits in terminal levels of sign-tracking. Furthermore, whereas ACb lesions primarily affected the probability of lever press responses, BLA lesions mostly affected the rate of responding once it occurred. Finally, disconnection lesions that disrupted communication between ACb and BLA produced both sets of deficits. We suggest that ACb is important for initial acquisition of consummatory-like responses that incorporate hedonic aspects of the reward, while BLA serves to enhance such incentive salience once it is acquired.

Highlights

► Rats with lesions of nucleus accumbens showed reduced probability of autoshaped lever pressing but only early in training. ► Rats with lesions of basolateral amygdala showed normal acquisition but reduced terminal rates of autoshaped lever pressing. ► Rats with asymmetrical disconnection lesions of both structures showed both deficits.

Introduction

An important consequence of associative learning is the acquisition of emotional and motivational responses (LeDoux, 2000, Rescorla and Holland, 1982, Rescorla and Solomon, 1967). For example, many investigators have asserted that Pavlovian conditioned stimuli (CSs) that predict food unconditioned stimuli (USs) acquire “incentive salience” reflecting the transfer of incentive motivational value from the US to the CS (Berridge, 2001, Berridge, 2004). Such CSs can reinforce new learning, as rats will learn to press a lever to receive CS presentations in the absence of the US (conditioned reinforcement; Mackintosh, 1974), and can modulate the performance of previously-rewarded instrumental responses (Pavlovian-instrumental transfer, PIT; Estes, 1948, Lovibond, 1983). Furthermore, certain food-paired cues can elicit approach and consummatory behaviors directed towards that CS, sometimes called “sign-tracking” (Boakes, 1977, Brown and Jenkins, 1968, Jenkins and Moore, 1973). For example, rats will approach visual cues paired with food delivery (Cardinal et al., 2002, Holland, 1977), and will approach and contact a lever whose insertion into the chamber signals food (Boakes, 1977, Flagel et al., 2009, Flagel et al., 2008, Kearns and Weiss, 2004). In contrast, rats may also direct their behavior toward the site of US delivery upon CS presentation, otherwise known as “goal-tracking” (Boakes, 1977, Flagel et al., 2008, Flagel et al., 2009).

Considerable attention has recently been focused on rats’ sign-tracking in an autoshaping (Brown & Jenkins, 1968) paradigm, in which the insertion of a lever into the experimental chamber is paired with the delivery of sucrose, regardless of the rats’ behavior. After repeated Pavlovian lever-sucrose pairings, rats come to press, grasp, and bite the lever as if it were sucrose itself (sign-tracking), despite the absence of any response–reward contingency (e.g., Tomie, 1996, Tomie et al., 2008). Although repeated CS–US pairings can result in both sign-tracking and goal-tracking CRs, some investigators have asserted that the sign-tracking (lever-directed) responses directly index the extent to which the lever CS becomes endowed with incentive salience (e.g., Flagel et al., 2009). For example, Robinson and Flagel (2009) reported that a lever insertion CS is more effective as a conditioned reinforcer in rats that showed high levels of sign-tracking responses during prior lever-food pairings than in rats that had primarily approached the food cup during lever insertions.

Many researchers have suggested that this paradigm may provide a valuable model for the study of incentive learning in drug addiction (e.g., Flagel et al., 2010, Mahler and Berridge, 2009, Tomie, 1996, Tomie et al., 2008). Autoshaping shares many of the behavioral characteristics associated with drug addiction such as persistence and relapse (Tomie et al., 2008), and high levels of sign-tracking responses have been associated with impulsivity, drug sensitization and other traits associated with addiction vulnerability (Flagel et al., 2010, Tomie et al., 2008). Furthermore, Flagel et al. (2011) found that sign-trackers but not goal-trackers showed increased phasic dopamine release in the nucleus accumbens (ACb) core in response to CS presentations, thus relating the sign-tracking response to brain systems frequently implicated in drug abuse and addiction (e.g., Everitt and Robbins, 2005, Robinson and Berridge, 2003).

Here we examined the roles of two brain regions known to be critical to incentive learning, ACb and the basolateral amygdala (BLA, Cador et al., 1989, Cardinal et al., 2002, Everitt et al., 2003, Parkinson et al., 2000, Parkinson et al., 2000), in learning and performance of discriminative autoshaped lever pressing in rats. Because both ACb core and shell have been found to be important for various learned incentive functions (Cardinal et al., 2002, Corbit and Balleine, 2011), we elected to lesion the entire ACb as a first step in determining its role in autoshaped lever pressing. We found that ACb lesions impaired the initial acquisition of sign-tracking but not its terminal levels. In contrast, BLA lesions produced substantial deficits in terminal levels of sign-tracking. Furthermore, whereas ACb lesions primarily affected the probability of lever press responses, BLA lesions mostly affected the rate of responding once it occurred. Finally, disconnection lesions that disrupted communication between ACb and BLA produced both sets of deficits.

Section snippets

Animals

The subjects were male Long-Evans rats (Charles River Laboratories, Raleigh, NC, USA), which weighed 300–325 g on arrival. Rats were individually housed in a climate controlled colony room that was illuminated from 7:00 A.M. to 7:00 P.M. Rats were given ad libitum access to food and water before and continuing two weeks after surgery. They were then placed on a food restriction schedule and maintained at 85% of their ad libitum weights throughout the autoshaping procedure.

Surgical procedures

Surgery was performed

Histological results

Fig. 1a presents a schematic representation of neuronal damage in accepted ACb-lesioned rats (n = 11). On average, 90.0 ± 4.9% (mean ± SEM) of ACb was eliminated, consisting of 93.0 ± 2.8% damage to ACbC and 87.6 ± 6.7% damage to ACbS. Data of rats with less than 50% damage to ACb were discarded. Sham-lesioned rats (n = 12) had no observable damage other than near the needle track. Fig. 1b and c shows sample neurotoxic and sham ACb lesions, respectively.

Autoshaped lever pressing

In contrast to conditioned ORs, which occur

Discussion

Our results show that ACb and BLA made distinct contributions to autoshaped lever pressing. Although rats with bilateral lesions of either ACb or BLA showed impairments in their acquisition or expression of autoshaping, they differed in both the timing and nature of those impairments (Experiments 1 and 2). Lesions of ACb reduced the probability of responding to the reinforced lever, but only early in training; by the end of training there was no significant difference in the probability of

Acknowledgment

This work was supported by NIH Grant MH53667.

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    Present address: Biomedical Sciences, PO Box 1881, Marquette University, Milwaukee, WI 3201, USA.

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