Effects of acute amphetamine exposure on two kinds of Pavlovian approach behavior

Holden, John Michael; Peoples, Laura L.

doi:10.1016/j.bbr.2009.11.014

Cited by 25 publications

(17 citation statements)

References 24 publications

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“…Following acute amphetamine, goal-tracking behavior was modestly but significantly increased in control rats relative to both antipsychotic-treated groups. This effect of amphetamine is consistent with previous work (Holden and Peoples, 2010). One possible explanation for the lack of effect of amphetamine in antipsychotic-treated rats is that a history of chronic antipsychotic exposure might alter the brain substrates underlying the expression of goaltracking behavior.…”

Section: Discussionsupporting

confidence: 81%

Continuous, but not Intermittent, Antipsychotic Drug Delivery Intensifies the Pursuit of Reward Cues

Bédard

Maheux

Lévesque

et al. 2011

Neuropsychopharmacol

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Chronic exposure to antipsychotic medications can persistently change brain dopamine systems. Most studies on the functional significance of these neural changes have focused on motor behavior and few have addressed how long-term antipsychotic treatment might influence dopamine-mediated reward function. We asked, therefore, whether a clinically relevant antipsychotic treatment regimen would alter the incentive motivational properties of a reward cue. We assessed the ability of a Pavlovian-conditioned stimulus to function as a conditioned reward, as well as to elicit approach behavior in rats treated with haloperidol, either continuously (achieved via subcutaneous osmotic minipump) or intermittently (achieved via daily subcutaneous injections). Continuous, but not intermittent, treatment enhanced the ability of amphetamine to potentiate the conditioned reinforcing effects of a cue associated with water. This effect was not related to differences in the ability to attribute predictive value to a conditioned stimulus (as measured by conditioned approach behavior), but was potentially linked to the development of behavioral supersensitivity to amphetamine and to augmented amphetamine-induced immediate early-gene expression (c-fos and Nur77) in dorsal striatopallidal and striatonigral cells. By enhancing the ability of reward cues to control behavior and by intensifying dopamine-mediated striatopallidal and striatonigral cell activity, standard (ie, continuous) antipsychotic treatment regimens might exacerbate drug-seeking and drug-taking behavior in schizophrenia. Achieving regular but transiently high antipsychotic levels in the brain (as modeled in the intermittent condition) might be a viable option to prevent these changes. This possibility should be explored in the clinic.

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Section: Discussionsupporting

confidence: 81%

Continuous, but not Intermittent, Antipsychotic Drug Delivery Intensifies the Pursuit of Reward Cues

Bédard

Maheux

Lévesque

et al. 2011

Neuropsychopharmacol

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“…Enhanced goal-tracking as a motivated response was interpreted as indicating that a third psychological component, namely, incentive salience targeted toward the dish, can potentially contribute to goal-tracking in some individuals, especially in states of mesocorticolimbic activation. Similarly, acute amphetamine administration has been reported to increase goal-tracking while drug is on board (Holden & Peoples, 2010). Finally, either amphetamine or opioid stimulation of nucleus accumbens can increase the relative incentive salience of a reward-proximal CS (analogous to the sucrose dish here) at the expense of a more predictive but reward-distal CS (analogous to the CS+ lever here) (Smith, Berridge, & Aldridge, 2011; Tindell, Berridge, Zhang, Peciña, & Aldridge, 2005).…”

Section: Discussionmentioning

confidence: 99%

Amphetamine-induced sensitization and reward uncertainty similarly enhance incentive salience for conditioned cues.

Robinson¹,

Anselme²,

Suchomel³

et al. 2015

Behavioral Neuroscience

105

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Amphetamine and stress can sensitize mesolimbic dopamine-related systems. In Pavlovian autoshaping, repeated exposure to uncertainty of reward prediction can enhance motivated sign-tracking or attraction to a discrete reward-predicting cue (lever CS+), as well as produce cross-sensitization to amphetamine. However, it remains unknown how amphetamine-sensitization or repeated restraint stress interact with uncertainty in controlling CS+ incentive salience attribution reflected in sign-tracking. Here rats were tested in three successive phases. First, different groups underwent either induction of amphetamine sensitization or repeated restraint stress, or else were not sensitized or stressed as control groups (either saline injections only, or no stress or injection at all). All next received Pavlovian autoshaping training under either certainty conditions (100% CS-UCS association) or uncertainty conditions (50% CS-UCS association and uncertain reward magnitude). During training, rats were assessed for sign-tracking to the lever CS+ versus goal-tracking to the sucrose dish. Finally, all groups were tested for psychomotor sensitization of locomotion revealed by an amphetamine challenge. Our results confirm that reward uncertainty enhanced sign-tracking attraction toward the predictive CS+ lever, at the expense of goal-tracking. We also report that amphetamine sensitization promoted sign-tracking even in rats trained under CS-UCS certainty conditions, raising them to sign-tracking levels equivalent to the uncertainty group. Combining amphetamine sensitization and uncertainty conditions together did not add together to elevate sign-tracking further above the relatively high levels induced by either manipulation alone. In contrast, repeated restraint stress enhanced subsequent amphetamine-elicited locomotion, but did not enhance CS+ attraction.

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“…Because larger dopamine transients evoked by food-predicting cues enhance the ability of these cues to promote food seeking [ 19 ], abused drugs augmenting extant dopamine transients should similarly drive ongoing appetitive behavior. Indeed, low-dose AMPH increases the amplitude and duration of dopamine transients evoked by cues predicting food reward [ 42 ] and enhances cue-driven food seeking [ 72 ]. It is interesting to speculate that these actions may also contribute to the efficacy of addictive DAT-Is as cognitive enhancers (see Outstanding Questions).…”

Section: Abused Drugs Augment Extant Dopamine Transients and Elicit Dmentioning

confidence: 99%

“…Whether activation of phasic dopamine signaling, as is described herein for cocaine and AMPH, contributes to clinical efficacy of DAT-Is is not known. The ability of AMPH to enhance associative learning [ 72 ] and augment dopamine transients [ 42 ] supports this possibility.…”

Section: Drug Addictionmentioning

confidence: 99%

Illicit dopamine transients: Reconciling actions of abused drugs

Covey

Roitman

Garris

2014

Trends in Neurosciences

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Phasic increases in brain dopamine are required for cue-directed reward seeking. While compelling within the framework of appetitive behavior, the view that illicit drugs hijack reward circuits by hyper-activating these dopamine transients is inconsistent with established psychostimulant pharmacology. However, recent work reclassifying amphetamine (AMPH), cocaine, and other addictive dopamine-transporter inhibitors (DAT-Is) supports transient hyper-activation as a unifying hypothesis of abused drugs. We argue here that reclassification also identifies generating burst firing by dopamine neurons as a keystone action. Unlike natural rewards, which are processed by sensory systems, drugs act directly on the brain. Consequently, to mimic natural reward and exploit reward circuits, dopamine transients must be elicited de novo. Of available drug targets, only burst firing achieves this essential outcome.

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Effects of acute amphetamine exposure on two kinds of Pavlovian approach behavior

Cited by 25 publications

References 24 publications

Continuous, but not Intermittent, Antipsychotic Drug Delivery Intensifies the Pursuit of Reward Cues

Continuous, but not Intermittent, Antipsychotic Drug Delivery Intensifies the Pursuit of Reward Cues

Amphetamine-induced sensitization and reward uncertainty similarly enhance incentive salience for conditioned cues.

Illicit dopamine transients: Reconciling actions of abused drugs

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