Dopamine, learning and motivation

Wise, Roy A.

doi:10.1038/nrn1406

Cited by 2,853 publications

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“…First, we used a drug self-administration procedure under fixed-ratio and PR schedules that has been employed to assess the reinforcing effects of nicotine and other drugs (Richardson and Roberts, 1996;Picciotto and Corrigall, 2002;Wise, 2004). We then used a reinstatement procedure to assess relapse to drug seeking induced by acute re-exposure to the self-administered drug or other stimuli following extinction of nicotine-maintained responding (Stewart, 2000;Le and Shaham, 2002;Shaham et al, 2003;Weiss, 2005).…”

Section: Discussionmentioning

confidence: 99%

Nicotine Self-Administration, Extinction Responding and Reinstatement in Adolescent and Adult Male Rats: Evidence Against a Biological Vulnerability to Nicotine Addiction during Adolescence

Shram

Funk

et al. 2007

Neuropsychopharmacol

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Initiation of smoking behavior typically occurs during adolescence and rarely occurs during adulthood. Despite this epidemiological evidence, relatively little is known about possible neurobiological differences in the response to nicotine in adolescents that might make them more vulnerable to nicotine addiction. In the current study, we assessed nicotine self-administration under fixed ratio (FR) and progressive ratio (PR) reinforcement schedules in adolescent (postnatal day (P) 33-35) and adult (P91-94) rats. We then assessed extinction and reinstatement of nicotine seeking in adulthood in rats that initiated nicotine self-administration during either adolescence or adulthood. Nicotine self-administration (0.03 mg/kg/infusion, i.v.) was higher in adult rats than in adolescent rats under FR5 and PR reinforcement schedules; no age differences in nicotine self-administration were observed under FR1 or FR2 reinforcement schedules. In contrast, saccharin self-administration under FR5 and PR reinforcement schedules was similar in both age groups, potentially ruling out age differences in general performance. Rats that initiated nicotine self-administration as adults demonstrated a greater resistance to extinction of nicotine taking behavior when saline was substituted for nicotine than rats that initiated self-administration as adolescents. Reinstatement of nicotine seeking following nicotine priming injections (0.075, 0.15, 0.3 mg/kg, s.c.) was independent of the age of onset of nicotine self-administration. The present data from established rat models of drug self-administration and drug relapse suggest that nicotine is less reinforcing in adolescent compared with adult rats and that processes other than the reinforcing effects of nicotine may be involved in the greater susceptibility to smoking during the adolescent developmental stage.

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Section: Discussionmentioning

confidence: 99%

Nicotine Self-Administration, Extinction Responding and Reinstatement in Adolescent and Adult Male Rats: Evidence Against a Biological Vulnerability to Nicotine Addiction during Adolescence

Shram

Funk

et al. 2007

Neuropsychopharmacol

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“…The dopaminergic system plays important roles in sensory-motor coordination, reward and motivation processes, and attention modulation. 12 Endogenous DA is synthesized in DA neurons and sequestered by vesicular monoamine transporter 2 (VMAT2) into synaptic vesicles ( Figure 1A). Upon exocytosis, DA is released to the synapse and the extrasynaptic space where it activates dopamine receptors.…”

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confidence: 99%

APP+, a Fluorescent Analogue of the Neurotoxin MPP+, Is a Marker of Catecholamine Neurons in Brain Tissue, but Not a Fluorescent False Neurotransmitter

Karpowicz

Dunn

Sulzer

et al. 2013

ACS Chem. Neurosci.

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ABSTRACT:We have previously introduced fluorescent false neurotransmitters (FFNs) as optical reporters that enable visualization of individual dopaminergic presynaptic terminals and their activity in the brain. In this context, we examined the fluorescent pyridinium dye 4-(4-dimethylamino)phenyl-1-methylpyridinium (APP+), a fluorescent analogue of the dopaminergic neurotoxin MPP+, in acute mouse brain tissue. APP+ is a substrate for the dopamine transporter (DAT), norepinephrine transporter (NET), and serotonin transporter (SERT), and as such represented a candidate for the development of new FFN probes. Here we report that APP+ labels cell bodies of catecholaminergic neurons in the midbrain in a DAT-and NET-dependent manner, as well as fine dopaminergic axonal processes in the dorsal striatum. APP+ destaining from presynaptic terminals in the dorsal striatum was also examined under the conditions inducing depolarization and exocytotic neurotransmitter release. Application of KCl led to a small but significant degree of destaining (approximately 15% compared to control), which stands in contrast to a nearly complete destaining of the new generation FFN agent, FFN102. Electrical stimulation of brain slices at 10 Hz afforded no significant change in the APP+ signal. These results indicate that the majority of the APP+ signal in axonal processes originates from labeled organelles including mitochondria, whereas only a minor component of the APP+ signal represents the releasable synaptic vesicular pool. These results also show that APP+ may serve as a useful probe for identifying catecholaminergic innervations in the brain, although it is a poor candidate for the development of FFNs.

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“…The involvement of both dopamine receptors families with learning and memory is widely reported for working memory [3], spatial learning [3,6], aversive memory [7], reward-related learning [8] and cognitive flexibility [9]. In particular, impairment in object recognition has been induced by D2 activity suppression due to haloperidol IP injection [10], by D1 activity suppression trough http://dx…”

Section: H I G H L I G H T Smentioning

confidence: 99%

“…Based on the D2 influence on learning and memory [8][9][10], we used haloperidol to induce OR impairment. At the time point of 30 min before exploration (B.E.)…”

mentioning

confidence: 99%

“…We also performed the difference between the group (vehicle or haloperidol) and the ratio = 1 (described above), t test against 1, to find out if the preference ratio presented by WT groups was significant different of the hypothesis of non-recognition of objects. To verify possible effects of haloperidol in the motor and motivation system [8,17] we measured the total distance traveled and the total time spent in object exploration.…”

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confidence: 99%

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Object recognition impairment and rescue by a dopamine D2 antagonist in hyperdopaminergic mice

França

Muratori

Nascimento

et al. 2016

Behavioural Brain Research

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h i g h l i g h t s• Heterozygous mice for dopamine transporter (DAT+/−) exhibit higher levels of synaptic dopamine.• Here we confirmed that D2 antagonism can interfere in object recognition.• We observed in DAT+/− a natural phenotype of impaired novel object memory recognition.• The injection of haloperidol at 0.05 mg before object exposition restored object recognition.• This effect could be explained by restoring D2 activity to optimal levels, acting on memory acquisition. a r t i c l e i n f o Genetically-modified mice without the dopamine transporter (DAT) are hyperdopaminergic, and serve as models for studies of addiction, mania and hyperactive disorders. Here we investigated the capacity for object recognition in mildly hyperdopaminergic mice heterozygous for DAT (DAT +/−), with synaptic dopaminergic levels situated between those shown by DAT −/− homozygous and wild-type (WT) mice. We used a classical dopamine D2 antagonist, haloperidol, to modulate the levels of dopaminergic transmission in a dose-dependent manner, before or after exploring novel objects. In comparison with WT mice, DAT +/− mice showed a deficit in object recognition upon subsequent testing 24 h later. This deficit was compensated by a single 0.05 mg/kg haloperidol injection 30 min before training. In all mice, a 0.3 mg/kg haloperidol injected immediately after training impaired object recognition. The results indicate that a mild enhancement of dopaminergic levels can be detrimental to object recognition, and that this deficit can be rescued by a low dose of a D2 dopamine receptor antagonist. This suggests that novel object recognition is optimal at intermediate levels of D2 receptor activity.© 2016 Elsevier B.V. All rights reserved.Dopamine (DA) is a neurotransmitter related to complex behaviors, such as: reward perception, social interaction [1,2], and is also linked to memory consolidation both in humans and rodents [3]. Alterations in DA synaptic regulation are related to a large variety of mental diseases, such as schizophrenia, hyperactivity, mood disorders, and Parkinson disease [4,5]. * Corresponding author.E-mail addresses: brunolobaosoares@gmail.com, brunolobaosoares@hotmail.com (B. Lobão-Soares).DA has many receptor subtypes, but they are basically divided in D1 and D2 families [3]. DA, mainly through D1 receptors, elicits the onset of the late phase of long term potentiation in the hippocampus [6], control plasticity-induced protein synthesis [6], and enhance the persistence of hippocampus-dependent memories [7].The involvement of both dopamine receptors families with learning and memory is widely reported for working memory [3], spatial learning [3,6], aversive memory [7], reward-related learning [8] and cognitive flexibility [9]. In particular, impairment in object recognition has been induced by D2 activity suppression due to haloperidol IP injection [10], by D1 activity suppression trough http://dx

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Dopamine, learning and motivation

Cited by 2,853 publications

References 184 publications

Nicotine Self-Administration, Extinction Responding and Reinstatement in Adolescent and Adult Male Rats: Evidence Against a Biological Vulnerability to Nicotine Addiction during Adolescence

Nicotine Self-Administration, Extinction Responding and Reinstatement in Adolescent and Adult Male Rats: Evidence Against a Biological Vulnerability to Nicotine Addiction during Adolescence

APP+, a Fluorescent Analogue of the Neurotoxin MPP+, Is a Marker of Catecholamine Neurons in Brain Tissue, but Not a Fluorescent False Neurotransmitter

Object recognition impairment and rescue by a dopamine D2 antagonist in hyperdopaminergic mice

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