Dopamine D3 receptor antagonists improve the learning performance in memory-impaired rats

Laszy, Judit; Laszlovszky, István; Gyertyán, István

doi:10.1007/s00213-004-2096-z

Cited by 127 publications

(81 citation statements)

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“…Recent studies showed that D 3 blockade has an important role in enhancing memory, attention, and learning (Nakajima et al, 2013). Moreover, D 3 antagonists were shown to improve learning deficits in memoryimpaired rats (Laszy et al, 2005). The current findings are, therefore, most likely to be attributed to a specific effect on the ability of conditioned stimuli, previously paired with the Figure 2 The effect of SB-277011-A (0.01-1 mg/ml/side), or vehicle (0), locally infused into the basolateral amygdala (BLA; n ¼ 7; a), nucleus accumbens (NAcc; n ¼ 8; b), or lateral habenula (LHb; n ¼ 7; c) on the mean (±SEM) number of active (filled symbols) or inactive (open symbols) lever presses during cue-induced reinstatement of nicotine seeking.…”

Section: Discussionmentioning

confidence: 99%

Dopamine D3 Receptors in the Basolateral Amygdala and the Lateral Habenula Modulate Cue-Induced Reinstatement of Nicotine Seeking

Khaled

Pushparaj

Ciano

et al. 2014

Neuropsychopharmacol

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Dopamine D 3 receptors are implicated in cue-induced relapse to drug seeking. We have previously shown that systemic administration of a selective D 3 antagonist reduces cue-induced reinstatement of nicotine seeking in rats. The current study sought to investigate potential neural substrates mediating this effect. The D 3 antagonist SB-277011-A (0.01-1 mg/0.5 ml/side) infused into the basolateral amygdala or the lateral habenula, but not the nucleus accumbens, significantly attenuated cue-induced reinstatement of nicotine seeking. Moreover, infusion of SB-277011-A (1 mg/0.5 ml/side) into the basolateral amygdala or lateral habenula had no effect on food selfadministration. Together with the finding that systemic SB-277011-A had no effect on extinction responding, this suggests that the effects observed here were on reinstatement and cue seeking, and not due to nonspecific motor activation or contextual-modified residual responding. The further finding of binding of [ 125 I]7-OH-PIPAT to D 3 receptors in the lateral habenula and in the basolateral amygdala is consistent with an important role of D 3 receptors in these areas in nicotine seeking. It was also found that systemic administration of the selective D 2 antagonist L741626 decreased cue-induced reinstatement, consistent with a role of D 2 and D 3 receptors in modulating this behavior. The current study supports an important role for D 3 receptors in the basolateral amygdala and lateral habenula in cue-induced reinstatement.

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Section: Discussionmentioning

confidence: 99%

Dopamine D3 Receptors in the Basolateral Amygdala and the Lateral Habenula Modulate Cue-Induced Reinstatement of Nicotine Seeking

Khaled

Pushparaj

Ciano

et al. 2014

Neuropsychopharmacol

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“…The role of hippocampal dysfunction in the PD recollection and recall impairment is specifically supported by rodent and imaging studies of healthy human adults, which show that the hippocampus and the ventral tegmental area form a functional loop controlling the entry of novel and salient/goal-directed information into long-term memory (e.g., Bethus, Tse, & Morris, 2010;Bunzeck, et al, 2007;Chowdhury, Guitart-Masip, Bunzeck, Dolan, & Duzel, 2012;Gasbarri, Sulli, & Packard, 1997; for a review see Lisman & Grace, 2005). Dopamine D1 and D2 receptors are also implicated in the persistence/slow consolidation of hippocampal-dependent memories (Hammad & Wagner, 2006;Laszy, Laszlovszky, & Gyertyan, 2005;Lisman, et al, 2011;O'Carroll, Martin, Sandin, Frenguelli, & Morris, 2006;Takahashi, et al, 2008) …”

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Evidence of an amnesia-like cued-recall memory impairment in nondementing idiopathic Parkinson's disease

Edelstyn

John

Shepherd

et al. 2015

Cortex

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Familiarity Medial temporal lobe Prefrontal cortexParkinson's disease a b s t r a c t Medicated, non-dementing mild-to-moderate Parkinson's disease (PD) patients usually show recall/recollection impairments but have only occasionally shown familiarity impairments. We aimed to assess two explanations of this pattern of impairment.Recollection typically improves when effortful planning of encoding and retrieval processing is engaged. This depends on prefrontally-dependent executive processes, which are often disrupted in PD. Relative to an unguided encoding and retrieval of words condition (C1), giving suitable guidance at encoding alone (C2) or at encoding and retrieval (C3) should, if executive processes are disrupted, improve PD recollection more than control recollection and perhaps raise it to normal levels. Familiarity, being a relatively automatic kind of memory, whether impaired or intact, should be unaffected by guidance. According to the second explanation, PD deficits are amnesia-like and caused by medial temporal lobe dysfunction and although poorer recollection, which is caused by hippocampal disruption, may be improved by guidance, it should not improve more than control recollection. Familiarity impairment will also occur if the perirhinal cortex is disrupted, but will be unimproved by guidance. Without guidance, recollection/ recall was impaired in thirty PD patients relative to twenty-two healthy controls and remained relatively equally impaired when full guidance was provided (C1 vs C3), both groups improving to broadly the same extent. Although impaired, and markedly less so than recollection, familiarity was not improved by guidance in both groups.The patients showed elevated rates of subclinical depressive symptoms, which weakly correlated with recall/recollection in all three conditions. PD executive function was also deficient and correlated with unguided/C1 recollection only. Our results are * Corresponding author. School of Psychology, Keele University, Keele, Staffordshire ST5 5BG, UK.E-mail address: n.edelstyn@keele.ac.uk (N.M.J. Edelstyn).Available online at www.sciencedirect.com ScienceDirectJournal homepage: www.elsevier.com/locate/cortex 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128

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“…Indeed, the use of D2/D3 family antagonists has been described for reducing the impairment of memory deficits induced by amnesic compounds in rodents [32]. This is also supported by the trend for OR facilitation in WT injected with 0.05 mg/kg haloperidol.…”

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confidence: 78%

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 D3 receptor antagonists improve the learning performance in memory-impaired rats

Abstract: These data suggest that dopamine D3 receptor antagonists possess cognition-enhancing activity which may be of benefit in the treatment of cognitive dysfunction associated with several psychiatric disorders.

Cited by 127 publications

References 37 publications

Dopamine D3 Receptors in the Basolateral Amygdala and the Lateral Habenula Modulate Cue-Induced Reinstatement of Nicotine Seeking

Dopamine D3 Receptors in the Basolateral Amygdala and the Lateral Habenula Modulate Cue-Induced Reinstatement of Nicotine Seeking

Evidence of an amnesia-like cued-recall memory impairment in nondementing idiopathic Parkinson's disease

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

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