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The Role of Accumbens Dopamine in Lever Pressing and Response Allocation: Effects of 6-OHDA Injected into Core and Dorsomedial Shell

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Abstract

Three experiments investigated the behavioral effects of injections of the neurotoxic agent 6-hydroxydopamine (6-OHDA) into the core or shell of the nucleus accumbens. In the first experiment, it was observed that injections of 6-OHDA into either core or shell had no significant effect on variable interval 30-s responding. In Experiment 2, responding on a fixed ratio 5 (FR5) schedule was impaired by 6-OHDA injections in the core, but not the shell. Rats with core injections of 6-OHDA showed significant alterations in the relative distribution of interresponse times, which were indicative of reductions in the maximal rate of responding and increases in the number of pauses. In the third experiment, rats were tested using a lever-pressing/chow-feeding procedure, in which a preferred food (Bioserve pellets) was available by pressing a lever on a FR5 schedule, but a less preferred food (lab chow) was also available concurrently in the test chamber. Untreated rats usually pressed the lever at high rates to obtain the food pellets and ate little of the lab chow. After training, dopamine depletions were produced by injections of 6-OHDA directly into the core or dorsomedial shell subregions. Injections of 6-OHDA into the core significantly decreased lever pressing for food pellets, increased lab chow consumption, and decreased the relative amount of food obtained by lever pressing. Dorsomedial shell injections of 6-OHDA had no significant effects on either lever pressing or lab chow consumption. Neurochemical results indicate that injections of 6-OHDA in the shell produced substantial depletions in the shell that were somewhat selective; however, injections of 6-OHDA into the core tended to deplete both core and shell. Correlational analyses revealed that decreases in FR5 lever pressing were associated with dopamine levels in the core, but not the shell. The present results indicate that substantial depletions of dopamine in the dorsomedial shell are not sufficient for suppressing reinforced lever pressing, and indicate that dopamine depletions must include the core area to impair performance on these tasks. The lack of effect of accumbens dopamine depletions on VI30 responding are consistent with the notion that accumbens dopamine depletions affect responding on schedules that generate a high rate of responding (FR5), but not those that generate a moderate rate of responding (e.g., VI30 s). The results of the concurrent FR5/chow-feeding experiment indicate that rats with accumbens dopamine depletions remain directed towards the acquisition and consumption of food. These results suggest that dopamine in the core region of accumbens sets constraints upon the selection of food-related behaviors, and that core dopamine depletions alter the relative allocation of food-related responses.

Section snippets

Subjects

A total of 90 male Sprague–Dawley rats (Harlan Sprague–Dawley, Indianapolis, IN) were used in these experiments. Rats were housed in a colony maintained at 23°C with a 12 L: 12 D cycle (lights on at 0700 h). Rats were initially food deprived to 85% of their free-feeding body weight, but then allowed a modest growth (up to 95% of original weight) over the course of the experiment. Water was available ad lib in the home cages.

Behavioral Procedures

Tests of lever pressing and chow consumption were conducted in operant

Neurochemical Results

As shown in Table 1, Table 2, Table 3, rats receiving injections of 6-OHDA in either the nucleus accumbens core or shell (see Fig. 1) had significant depletions of DA in both regions, as demonstrated by ANOVA. For the analysis of nucleus accumbens core DA, ANOVA revealed an overall significant effect of the 6-OHDA treatment in all three experiments [Table 1, F(2, 24) = 88.67, p < 0.001; Table 2, F(2, 21) = 26.91, p < 0.001; Table 3, F(2, 22) = 23.99, p < 0.001]. For all three experiments,

Discussion

In these experiments it was observed that the behavioral effects of injections of 6-OHDA into the nucleus accumbens can vary greatly, depending upon the site of injection and the behavioral task employed. There were no significant effects of core or shell 6-OHDA injections on VI30 responding. Following core injections of 6-OHDA, lever pressing on the FR5 schedule was significantly decreased, and the distribution of IRTs was substantially altered. On the concurrent FR5/chow feeding task, core

Acknowledgements

This research was supported by a grant from the National Science Foundation. Many thanks to Juliet Aberman for her helpful comments.

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