Selective Blockade of Dopamine D3 Receptors Enhances while D2 Receptor Antagonism Impairs Social Novelty Discrimination and Novel Object Recognition in Rats: A Key Role for the Prefrontal Cortex

Watson, David J.; Loiseau, Florence; Ingallinesi, Manuela; Millan, Mark J.; Marsden, C.A.; Fone, Kevin C. F.

doi:10.1038/npp.2011.254

Cited by 147 publications

(129 citation statements)

References 85 publications

Supporting

Mentioning

122

Contrasting

Order By: Relevance

“…They also found that the deficit observed by blocking the VTA could be rescued by infusing the D1 receptor agonist SKF38397 into the mPFC. By using a similar microinjection approach in the mPFC we have also shown that blockade of dopamine D 3 receptors enhances, while D 3 receptor activation or antagonism of dopamine D 2 receptors impairs NOR in the rat (Watson et al 2012). Taken together these findings, which demonstrate the importance of dopamine neurotransmission in the mPFC for NOR consolidation, are also consistent with our findings.…”

Section: Discussionsupporting

confidence: 91%

Role of the anterior cingulate cortex in the retrieval of novel object recognition memory after a long delay

et al. 2017

View full text Add to dashboard Cite

Previous in vivo electrophysiological studies suggest that the anterior cingulate cortex (ACgx) is an important substrate of novel object recognition (NOR) memory. However, intervention studies are needed to confirm this conclusion and permanent lesion studies cannot distinguish effects on encoding and retrieval. The interval between encoding and retrieval tests may also be a critical determinant of the role of the ACgx. The current series of experiments used micro-infusion of the GABAA receptor agonist, muscimol, into ACgx to reversibly inactivate the area and distinguish its role in encoding and retrieval. ACgx infusions of muscimol, before encoding did not alter NOR assessed after a delay of 20 min or 24 h. However, when infused into the ACgx before retrieval muscimol impaired NOR assessed after a delay of 24 h, but not after a 20-min retention test. Together these findings suggest that the ACgx plays a time-dependent role in the retrieval, but not the encoding, of NOR memory, neuronal activation being required for the retrieval of remote (24 h old), but not recent (20 min old) visual memory.

show abstract

Section: Discussionsupporting

confidence: 91%

Role of the anterior cingulate cortex in the retrieval of novel object recognition memory after a long delay

et al. 2017

View full text Add to dashboard Cite

show abstract

“…However, long term blockade of D2 receptors can lead to increased dopamine release and the activation of other dopamine receptors [52]. Thee higher availability of D3 receptors would thus be consistent with the observation that stimulation of D3 receptors impairs performance in the novel object test [53]. Furthermore, stimulation of D4 receptors was found to stimulate object exploration [54] as was observed in sulpiride-treated mice.…”

Section: Reducing Motivation For Exercise Has Limited Behavioural Impactsupporting

confidence: 78%

Corticosterone and dopamine D2/D3 receptors mediate the motivation for voluntary wheel running in C57BL/6J mice

Ebada

Kendall

Pardon

2016

Behavioural Brain Research

View full text Add to dashboard Cite

Number of tables: 1Number of words in the abstract: 248Number of words in the manuscript (including tables and figure legends): 6,639Number of words in the introduction: 1,290Number of words in the discussion: 1,243 ABSTRACT Physical exercise can improve cognition but whether this is related to motivation levels is unknown. Voluntary wheel running is a rewarding activity proposed as a model of motivation to exercise. To question the potential effects of exercise motivation on subsequent behaviour, we used a pharmacological approach targeting some reward mechanisms. The stress hormone corticosterone has rewarding effects mediated by activation of low affinity glucocorticoid receptors (GR). To investigate whether corticosterone synthesis motivates exercise via activation of GRs and subsequently, impacts on behaviour, we treated C57BL/6J mice acutely with the inhibitor of corticosterone synthesis metyrapone (35 mg/kg) or repeatedly with the GR antagonist mifepristone (30 mg/kg) prior to 1-hour running wheel sessions. To investigate whether reducing motivation to exercise impacts on behaviour, we antagonised running-induced dopamine D2/D3 receptors activation with sulpiride (25 or 50 mg/kg) and assessed locomotor, anxiety-related and memory performance after 20 running sessions over 4 weeks. We found that corticosterone synthesis contributes to running levels, but the maintenance of running behaviour was not mediated by activation of GRs. Intermittent exercise was not associated with changes in behavioural or cognitive performance. The persistent reduction in exercise levels triggered by sulpiride also had limited impact on behavioural performance, although the level of performance for some behaviours was related to the level of exercise. Altogether, these findings indicate that corticosterone and dopamine D2/D3 receptor activation contribute to the motivation for wheel running, but suggest that motivation for exercise is not a sufficient factor to alter behaviour in healthy mice.

show abstract

“…Thus, it is possible that loss of M 1 -mediated mLTD at the hippocampo-PFC synapse plays a major role in regulating PFC activation by hippocampal afferents under normal conditions, and that loss of this function contributes to the increased activation of the PFC and resultant behavioral outcomes of dysfunctional recognition memory and social interaction in this rodent model. As normal PFC function is essential for both social interaction (Elliott et al, 2012;Shah and Treit, 2003;Wall et al, 2012) and recognition memory (Bekinschtein and Weisstaub, 2014;Watson et al, 2012) in rodents, this study provides the first direct evidence for a potential role of impaired M 1 -mediated mLTD in PFC as an underlying cause of these behavioral deficits.…”

Section: Role Of M 1 Pam In Pcp-treated Micementioning

confidence: 70%

Potentiation of M1 Muscarinic Receptor Reverses Plasticity Deficits and Negative and Cognitive Symptoms in a Schizophrenia Mouse Model

Ghoshal

Rook

Dickerson

et al. 2015

Neuropsychopharmacol

122

View full text Add to dashboard Cite

Schizophrenia patients exhibit deficits in signaling of the M 1 subtype of muscarinic acetylcholine receptor (mAChR) in the prefrontal cortex (PFC) and also display impaired cortical long-term depression (LTD). We report that selective activation of the M 1 mAChR subtype induces LTD in PFC and that this response is completely lost after repeated administration of phencyclidine (PCP), a mouse model of schizophrenia. Furthermore, discovery of a novel, systemically active M 1 positive allosteric modulator (PAM), VU0453595, allowed us to evaluate the impact of selective potentiation of M 1 on induction of LTD and behavioral deficits in PCP-treated mice. Interestingly, VU0453595 fully restored impaired LTD as well as deficits in cognitive function and social interaction in these mice. These results provide critical new insights into synaptic changes that may contribute to behavioral deficits in this mouse model and support a role for selective M 1 PAMs as a novel approach for the treatment of schizophrenia.

show abstract

Selective Blockade of Dopamine D3 Receptors Enhances while D2 Receptor Antagonism Impairs Social Novelty Discrimination and Novel Object Recognition in Rats: A Key Role for the Prefrontal Cortex

Cited by 147 publications

References 85 publications

Role of the anterior cingulate cortex in the retrieval of novel object recognition memory after a long delay

Role of the anterior cingulate cortex in the retrieval of novel object recognition memory after a long delay

Corticosterone and dopamine D2/D3 receptors mediate the motivation for voluntary wheel running in C57BL/6J mice

Potentiation of M1 Muscarinic Receptor Reverses Plasticity Deficits and Negative and Cognitive Symptoms in a Schizophrenia Mouse Model

Contact Info

Product

Resources

About