Seeking–taking chain schedules of cocaine and sucrose self-administration: effects of reward size, reward omission, and α-flupenthixol

Veeneman, M. M. J.; Ast, M. van; Broekhoven, Mark H.; Limpens, Jules H. W.; Vanderschuren, Louk J. M. J.

doi:10.1007/s00213-011-2525-8

Cited by 23 publications

(19 citation statements)

References 79 publications

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“…This signal is considered important for the acquisition of complex reward-seeking behaviors (21, 22). Interestingly, dopamine receptor blockade has recently been shown to reduce response likelihood during a self-initiated reward-seeking action sequence (23) and accumbal dopamine depletions disrupt action performance when many actions are required to obtain reward (24), which is consistent with a large literature implicating dopamine in incentive motivation (25, 26), the process that allows reward-predictive cues to invigorate reward-seeking actions. Such findings raise the possibility that task-related dopamine signaling also exerts a motivational influence over reward-seeking actions.…”

supporting

confidence: 55%

Phasic Mesolimbic Dopamine Signaling Precedes and Predicts Performance of a Self-Initiated Action Sequence Task

Wassum

Ostlund

Maidment

2012

Biological Psychiatry

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Background Sequential reward-seeking actions are readily learned despite the temporal gap between the earliest (distal) action in the sequence and the reward delivery. Fast dopamine signaling is hypothesized to mediate this form of learning by reporting errors in reward prediction. However, such a role for dopamine release in voluntarily initiated action sequences remains to be demonstrated. Methods Using fast-scan cyclic voltammetry we monitored phasic mesolimbic dopamine release, in real-time, as rats performed a self-initiated sequence of lever presses to earn sucrose rewards. Prior to testing rats received either 0 (n=11), 5 (n=11) or 10 (n=8) days of action sequence training. Results For rats acquiring the action sequence task at test dopamine release was strongly elicited by response-contingent (but unexpected) rewards. With learning, a significant elevation in dopamine release preceded performance of the proximal action, and subsequently came to precede the distal action. This pre-distal dopamine release response was also observed in rats previously trained on the action sequence task, and the amplitude of this signal predicted the latency with which rats completed the action sequence. Importantly, the dopamine response to contingent reward delivery was not observed in rats given extensive pre-training. Pharmacological analysis confirmed that task performance was dopamine dependent. Conclusions These data suggest that phasic mesolimbic dopamine release mediates the influence that rewards exert over the performance of self-paced, sequentially-organized behavior and shed light on how dopamine signaling abnormalities may contribute to disorders of behavioral control.

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supporting

confidence: 55%

Phasic Mesolimbic Dopamine Signaling Precedes and Predicts Performance of a Self-Initiated Action Sequence Task

Wassum

Ostlund

Maidment

2012

Biological Psychiatry

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“…The present data are reminiscent of those observed after administration of dopamine receptor antagonists during psychostimulant self-administration. In those experiments, reducing the reinforcing properties of cocaine with a dopamine receptor antagonist led to a decrease in breakpoint under a progressive ratio schedule of reinforcement, which coincided with increased responding under a fixed-ratio schedule of reinforcement, as if to compensate for the reduced subjective effects of the drug [44]–[46]. Future experiments should elucidate whether altered appetitive, hedonic or reinforcing properties of sucrose underlies the effects of lShell DBS on operant responding for sucrose.…”

Section: Discussionmentioning

confidence: 98%

Deep Brain Stimulation Reveals a Dissociation of Consummatory and Motivated Behaviour in the Medial and Lateral Nucleus Accumbens Shell of the Rat

et al. 2012

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Following the successful application of deep brain stimulation (DBS) in the treatment of Parkinson's disease and promising results in clinical trials for obsessive compulsive disorder and major depression, DBS is currently being tested in small patient-populations with eating disorders and addiction. However, in spite of its potential use in a broad spectrum of disorders, the mechanisms of action of DBS remain largely unclear and optimal neural targets for stimulation in several disorders have yet to be established. Thus, there is a great need to examine site-specific effects of DBS on a behavioural level and to understand how DBS may modulate pathological behaviour. In view of the possible application of DBS in the treatment of disorders characterized by impaired processing of reward and motivation, like addiction and eating disorders, we examined the effect of DBS of the nucleus accumbens (NAcc) on food-directed behavior. Rats were implanted with bilateral stimulation electrodes in one of three anatomically and functionally distinct sub-areas of the NAcc: the core, lateral shell (lShell) and medial shell (mShell). Subsequently, we studied the effects of DBS on food consumption, and the motivational and appetitive properties of food. The data revealed a functional dissociation between the lShell and mShell. DBS of the lShell reduced motivation to respond for sucrose under a progressive ratio schedule of reinforcement, mShell DBS, however, profoundly and selectively increased the intake of chow. DBS of the NAcc core did not alter any form of food-directed behavior studied. DBS of neither structure affected sucrose preference. These data indicate that the intake of chow and the motivation to work for palatable food can independently be modulated by DBS of subregions of the NAcc shell. As such, these findings provide important leads for the possible future application of DBS as a treatment for eating disorders such as anorexia nervosa.

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“…Some investigators maintain that the DLS is just as important as the NAc in the reinforcing effects of cocaine in early stages of cocaine addiction (Veeneman et al, 2012), while others have postulated that the progression from voluntary to compulsive drug use involves a transition from prefrontal cortical and NAc control to mediation by the dorsal striatum (Dalley et al, 2011, Everitt and Robbins, 2005). The results presented here demonstrate that estradiol can rapidly enhance cocaine’s neurobiological effects in DLS in females but not males, as has been previously reported for amphetamine (Castner et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Sex differences in the effects of estradiol in the nucleus accumbens and striatum on the response to cocaine: Neurochemistry and behavior

Cummings

Jagannathan

Jackson

et al. 2014

Drug and Alcohol Dependence

101

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Background Females exhibit more rapid escalation of cocaine use and enhanced cocaine-taking behavior as compared to males. While ovarian hormones likely play a role in this increased vulnerability, research has yet to examine the role of estradiol in affecting the behavioral and neurological response to cocaine in a brain region- and sex-specific way. Methods First, we examined stereotypy and locomotor sensitization after repeated cocaine administration (10 mg/kg i.p.) in intact (SHAM) and castrated (CAST) males, and ovariectomized (OVX) females treated with 5 μg estradiol benzoate (EB) or vehicle (OIL). Next, we used in vivo microdialysis to examine the effects of acute EB treatment on cocaine-induced DA in the regions mediating the display of these behaviors (i.e., the dorsolateral striatum, DLS; and the nucleus accumbens, NAc; respectively). Results We find that EB enhances sensitization of cocaine-induced stereotypy in OVX females after 12 days of cocaine treatment, and after a 10-day withdrawal. Similarly, the OVX/EB females show enhanced locomotor sensitization compared to the other three groups on the same days. Using in vivo microdialysis to assess the neurochemical response, we find that EB rapidly enhances cocaine-induced DA in DLS dialysate of OVX females but not CAST males, and has no effect in NAc of either sex. Conclusions With these experiments, we show that there are sex differences in the effects of estradiol to preferentially enhance the response to cocaine in the DLS over the NAc in females, which may contribute to the preferential sensitization of stereotypy in females.

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Seeking–taking chain schedules of cocaine and sucrose self-administration: effects of reward size, reward omission, and α-flupenthixol

Cited by 23 publications

References 79 publications

Phasic Mesolimbic Dopamine Signaling Precedes and Predicts Performance of a Self-Initiated Action Sequence Task

Phasic Mesolimbic Dopamine Signaling Precedes and Predicts Performance of a Self-Initiated Action Sequence Task

Deep Brain Stimulation Reveals a Dissociation of Consummatory and Motivated Behaviour in the Medial and Lateral Nucleus Accumbens Shell of the Rat

Sex differences in the effects of estradiol in the nucleus accumbens and striatum on the response to cocaine: Neurochemistry and behavior

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