Elsevier

Physiology & Behavior

Volume 76, Issue 3, July 2002, Pages 379-387
Physiology & Behavior

Nucleus accumbens cell firing during goal-directed behaviors for cocaine vs. ‘natural’ reinforcement

https://doi.org/10.1016/S0031-9384(02)00760-6Get rights and content

Abstract

Numerous investigations indicate that the nucleus accumbens (Acb) is an important neural substrate mediating the reinforcing properties of ‘natural’ rewards (food or water) as well as abused substances. Here, our electrophysiological studies that examined Acb cell firing within seconds of lever press responding for intravenous cocaine vs. water or food reinforcement in rats are reviewed. Initial investigations revealed that a subset of Acb neurons exhibits four types of firing patterns within seconds of the reinforced response for intravenous cocaine during self-administration sessions. Three of those four cell types were also observed during water reinforcement sessions. In a subsequent study, the activity of the same Acb neurons was examined in rats responding on multiple schedules for either two distinct ‘natural’ reinforcers (water and food), or one of those ‘natural’ reinforcers and the intravenous self-administration of cocaine. The results showed that the majority of neurons tested exhibited similar, overlapping neuronal firing patterns across the two ‘natural’ reinforcer conditions. In contrast, the majority of neurons examined displayed differential, nonoverlapping firing patterns relative to operant responding for water (or food) vs. cocaine reinforcement. Additional studies that examined the role of associative factors on Acb cell firing during cocaine self-administration sessions are reviewed. Collectively, these findings illustrate the dynamic nature of Acb cell firing in behaving animals, and provide insight into how Acb neurons process information about goal-directed behaviors for ‘natural’ reinforcers vs. abused substances.

Introduction

A number of studies have indicated that the nucleus accumbens (Acb) is critically involved in mediating the reinforcing properties of ‘natural’ reinforcers such as food, water and sex. For example, feeding behavior is induced in rats via microinfusion of non-NMDA glutamate receptor antagonists or GABA agonists into the shell region of the Acb [24], [25], [47], [48]. In addition, microdialysis studies have shown increased dopamine levels in the Acb during feeding, drinking and sexual behaviors in rats [2], [18], [39], [49], [50]. Likewise, the dopaminergic projection from the ventral tegmental area (VTA) to the Acb appears to be a crucial neural substrate through which abused substances such as cocaine exert their reinforcing actions [5], [26], [27], [51], [52], [53], [54]. For example, selective dopamine lesions of the VTA or Acb using 6-OHDA resulted in significant decreases in cocaine self-administration in rats [37], [40], [41], as did destruction of Acb cell bodies using the neurotoxin kainic acid [55]. Furthermore, microdialysis studies have shown increased dopamine levels in the Acb during cocaine self-administration sessions in rats [23], [38], [54].

Studies employing electrophysiological recording procedures in behaving animals also support a role of the Acb in mediating the reinforcing properties of ‘natural’ rewards and drugs of abuse. One important advantage of this technique is the high degree of temporal resolution of Acb activity that allows for a characterization of Acb cell firing at critical times during goal-directed behaviors (e.g., lever press for reward). In this regard, it has been shown that distinct populations of Acb neurons exhibit changes in cell firing (increases and/or decreases) relative to operant responding for juice reinforcement in monkeys [3], [22], [43], [44] and water or food reinforcement in rats [7], [11], [28]. Likewise, studies have shown that a subset of Acb neurons displays patterned discharges relative to the cocaine-reinforced response during self-administration sessions in rats. Specifically, Acb neurons have been shown to exhibit changes (increases and/or decreases) in cell firing within seconds of the reinforced response for intravenous cocaine, or cycle on the order of minutes within the entire interinfusion interval (INT) [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [30], [33], [34], [35], [36]. Therefore, using this approach, underlying cellular mechanisms mediating behaviors associated with drug or ‘natural’ reinforcement have been uncovered.

Here, our electrophysiological studies that examined Acb cell firing within seconds of operant responding for ‘natural’ reinforcement vs. intravenous cocaine are reviewed. In addition, experiments that explored the associative properties of Acb cell firing during cocaine self-administration sessions are described. For example, our studies have revealed that a subset of Acb neurons is activated during response-independent presentations of stimuli previously paired with cocaine delivery during self-administration sessions. Collectively, these studies illustrate the highly dynamic properties of Acb cell firing in behaving animals related to the nature of the reinforcer (‘natural’ vs. drug) and the environmental context associated with reward.

Section snippets

Initial findings

In our initial set of experiments, Acb cell firing was examined during water reinforcement and cocaine self-administration sessions completed during different behavioral sessions (i.e., the same cell was not examined across the two reinforcer conditions). During self-administration sessions, animals were trained to press a lever on a fixed ratio 1 (FR1) schedule of reinforcement for the intravenous infusion of cocaine (0.33 mg infused over 6 s). The beginning of the session was signaled by the

Associative properties of accumbens cell firing

The above findings illustrate the dynamic nature of Acb cell firing in behaving rats in that populations of Acb cells selectively encode information about cocaine or ‘natural’ reward. An important issue we addressed in another series of experiments is whether the activity of Acb neurons that process information about cocaine reinforcement is influenced by the presentation of stimuli associated with drug reward. Such an activation of Acb neurons by cocaine-associated stimuli may be relevant with

Summary and unresolved issues

The findings described above reveal several important properties of Acb cell firing during goal-directed behaviors in rats. The results indicate that a subset of Acb neurons exhibits distinct types of patterned discharges that are synchronized to the lever press response that result in drug or ‘natural’ reinforcement. Neurons exhibit complementary firing patterns that collectively encode the entire sequence of the reinforced response including response initiation, response execution and

Acknowledgements

This research was supported by NIDA DA10006, DA14339 and The Whitehall Foundation.

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