Abstract

INTRODUCTION

REWARD-RELEVANT CHANGES IN NAcc DA TRANSMISSION

CONCLUSIONS

Discussion
Board

We used voltammetry and monoamine-selective probes to monitor dopamine (DA) transmission in nucleus accumbens (NAcc) of rats lever-pressing for food. Under standard conditions, animals responded on a fixed ratio (FR) 1 schedule for 0.2 ml of milk delivered over 30 sec; milk delivery was paired with a 30 sec cue light. Consumption of the initial few milk rewards of the session caused DA signal increases. These initial signal increases were typical of the first and at times the second test days. On subsequent days, however, the most pronounced initial signal increases coincided with presentation of conditioned stimuli that marked the start of the session. Biphasic changes in DA signal that were time-locked to each reinforced lever-press were also observed; responses were preceded by increases and were followed, during milk consumption, by decreases in DA signal. At the end of milk delivery, the signal increased again in apparent anticipation of the next lever-press. Delaying milk delivery caused a corresponding delay in DA signal decreases and the amount of time signals remained depressed was bound by the duration of milk consumption. Greater decreases in DA signal were observed when the rate of milk delivery was doubled or tripled and such increases in reward value were associated with more pronounced signal increases during the period that preceded each lever-press. In contrast, DA signal increases were seen when milk was delivered at half the usual rate or was withheld altogether or when animals were denied access to the lever. Under partial reinforcement conditions, reinforced lever-presses were preceded by more pronounced signal increases and decreases of comparable magnitude accompanied milk consumption. These results suggest that meso-NAcc DA neurons are activated primarily in response to the incentive rather than to the reinforcing properties of rewards. While the present data indicate that food reinforcement can activate the DA projection to NAcc, this effect was found to be transient. One working hypothesis suggested by the present findings is that rewards produce their behavior reinforcing effects as a consequence of suppressing activation of meso-NAcc DA neurons by conditioned incentives. Exactly what mechanism would be responsible for exerting this inhibitory influence is open to speculation. The medial prefrontal cortex (PFC), however, is one possibility made increasingly attractive by evidence that meso-PFC DA neurons act indirectly, via corticofugal inputs to VTA and NAcc, to dampen concurrent increases in NAcc DA transmission. As a first step in exploring this possibility, we investigated how PFC DA levels change in relation to earned food presented under conditions identical to those tested in NAcc DA. In comparison to NAcc, we observed minor DA signal fluctuations in PFC when animals consumed the standard reward on a continuous reinforcement schedule; there was no evidence of experience-dependent changes in these fluctuations. Under delayed reinforcement conditions, lever-presses were followed by DA signal increases that were time-locked to the delay duration and these were followed by signal decreases when animals eventually received the reward. Such decreases became more pronounced when the standard rate of milk delivery was tripled, but were attenuated when milk delivery was reduced to half the usual rate; withholding earned milk resulted in signal increases. In contrast, DA signal increases were observed during milk consumption when the standard meal duration was unexpectedly shortened to 15 sec or lengthened to 60 or 90 sec. Orderly changes in DA signal were also observed under partial reinforcement conditions; unreinforced responses were associated with DA signal decreases whereas transient increases were seen during the 30 sec meal that followed reinforced responses. These findings indicate that response-contingent reward presentation elicits synchronous changes in PFC DA transmission. They also suggest that the DA input to PFC is activated primarily when rewards are presented under conditions that deviate from those animals had come to expect, particularly so when the temporal structure of learned associations is altered. Such a conclusion would be congruent with the idea that PFC DA plays a role in cognitive processes responsible for the temporal organization of goal-directed behaviors. Finally, the present findings suggest that some of the reward- and behavior-relevant changes seen in NAcc DA may occur as a result of concurrent fluctuations in PFC DA levels. Supported by the Medical Research Council of Canada.

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Presentation Number SAgratton0867
Keywords: nucleus accumbens, prefrontal cortex, motivation, incentive, working memory