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
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Dopamine D(3) receptor antagonists exert pro-cognitive effects in both rodents and primates. Accordingly, this study compared the roles of dopamine D(3) vs D(2) receptors in social novelty discrimination (SND), which relies on olfactory cues, and novel object recognition (NOR), a visual-recognition task. The dopamine D(3) receptor antagonist, S33084 (0.04-0.63 mg/kg), caused a dose-related reversal of delay-dependent impairment in both SND and NOR procedures in adult rats. Furthermore, mice genetically deficient in dopamine D(3) receptors displayed enhanced discrimination in the SND task compared with wild-type controls. In contrast, acute treatment with the preferential dopamine D(2) receptor antagonist, L741,626 (0.16-5.0 mg/kg), or with the dopamine D(3) agonist, PD128,907 (0.63-40 μg/kg), caused a dose-related impairment in performance in rats in both tasks after a short inter-trial delay. Bilateral microinjection of S33084 (2.5 μg/side) into the prefrontal cortex (PFC) of rats increased SND and caused a dose-related (0.63-2.5 μg/side) improvement in NOR, while intra-striatal injection (2.5 μg/side) had no effect on either. In contrast, bilateral microinjection of L741,626 into the PFC (but not striatum) caused a dose-related (0.63-2.5 μg/side) impairment of NOR. These observations suggest that blockade of dopamine D(3) receptors enhances both SND and NOR, whereas D(3) receptor activation or antagonism of dopamine D(2) receptor impairs cognition in these paradigms. Furthermore, these actions are mediated, at least partly, by the PFC. These data have important implications for exploitation of dopaminergic mechanisms in the treatment of schizophrenia and other CNS disorders, and support the potential therapeutic utility of dopamine D(3) receptor antagonism.
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Pre-sample microinjections of the DA D2-R antagonist L-741.626 into the PFC dose-dependently disrupted short-term NOP (2 min interval).
“Pre-sample microinjections of the DA D2-R antagonist L-741.626 into the PFC dose-dependently disrupted short-term NOP (2 min interval), which is consistent with its effects with acute systemic administration (Watson et al., 2012).”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as Watson et al., 2012
Pre-sample infusions of the D3-R antagonist S33084 into the rat PFC dose-dependently improved NOP (4 hours interval).
“Pre-sample infusions of the D3-R antagonist S33084 into the rat PFC dose-dependently improved NOP (4 hours interval), supported by the findings when injected systemically (Watson et al., 2012).”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as Watson et al., 2012
NOP memory tested even minutes later was impaired by pre-sample infusions of substances into the PFC.
“Furthermore, pharmacological studies have found that NOP memory tested even minutes later was impaired by pre-sample infusions of substances into the PFC (Christoffersen et al., 2008; Pezze et al., 2015; Watson et al., 2012).”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as Watson et al., 2012
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References 89 · Cited by 151
- Authors
- Watson, D. J., Loiseau, F., Ingallinesi, M., Millan, M. J., Marsden, C. A., & Fone, K. C.
- Affiliations
- University of Nottingham (GB)
- Institut de Recherches Internationales Servier (France) (FR)
- Corresponding author
- Fone, Kevin CF
- Venue
- Neuropsychopharmacology
- Published
- 2011-10-26
- Volume
- 37
- Issue
- 3
- Pages
- 770-786
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3261029
- OpenAlex
- W2034006349
- Cited by
- 151
- References
- 89
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 8 · 2023: 10 · 2022: 13 · 2021: 8 · 2020: 12 · 2019: 11 · 2018: 7 · 2017: 19 · 2016: 11 · 2015: 18 · 2014: 8 · 2013: 12 · 2012: 6
- FWCI
- 3.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
- Funders
- Servier
- Institut de Recherches Servier
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- dopamine D3 receptor, dopamine D2 receptor, novel object recognition, prefrontal cortex, cognitive enhancement, odor discrimination, visual recognition memory, striatum, schizophrenia, dopaminergic mechanisms
- MeSH terms
- Animals, Benzopyrans, Discrimination, Psychological, Dose-Response Relationship, Drug, Indoles, Male, Microinjections, Piperidines, Pyrroles, Rats, Wistar, Prefrontal Cortex, Receptors, Dopamine D2, Mice, Knockout, Dopamine Antagonists, Recognition, Psychology, Receptors, Dopamine D3, Mice, Rats, Dopamine D2 Receptor Antagonists
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